Neutrophil percentages in bronchoalveolar lavage fluid: Implications for diagnosing bacterial pneumonia in patients with immunocompromise and neutropenia.

Background: Pneumonia is the leading cause of infectious deaths and the most common infection identified in ICU patients. Assessment of bronchoalveolar lavage fluid (BALF) cellularity can aid in pneumonia diagnosis. Low percentages (<50%) of BALF neutrophils have a high negative predictive value for bacterial pneumonia in a general medical ICU population, but unclear operating characteristics in patients with immunocompromise and neutropenia remain unknown. Methods: We analyzed a large cohort of BALF specimens obtained for routine care for suspected pneumonia in mechanically ventilated patients and enrolled in the single-center Successful Clinical Response In Pneumonia Therapy (SCRIPT) study. BALF neutrophils were reported as a percentage of leukocytes by the clinical laboratory. The etiology of each episode of suspected pneumonia was adjudicated by a committee of critical care physicians using a predefined protocol. Immunocompromise was defined using predetermined criteria by the study research team. Neutropenia was defined here as a peripheral ANC <1500 cells/µl. Data are expressed as median [Quartile (Q) 1, Q3] and compared using the Mann-Whitney U test. Results: 688 mechanically ventilated patients with suspected pneumonia were included. 409 (59.4%) were male; median age was 62 [51,71]. 461 patients (67.0%) were immunocompetent, 149 (21.7%) were immunocompromised without neutropenia and 78 (11.3%) were neutropenic at some point during their admission. A total of 1746 BALs were performed. Fifty-seven BALs were obtained on a day where the patient's ANC<1500. Amongst pneumonia episodes classified as bacterial, no difference was found amongst BALF percent neutrophils taken patients who were immunocompetent and those who were immunocompromised but not neutropenic on day of sampling: 84.0% [69.0, 93.0] vs 87.0% [68.3, 93.0], p = 0.878 (Figure 1B). However, BALF percent neutrophils were significantly lower in patients neutropenic on day of sampling, with median BALF percent neutrophils of only 65.0% [22.3, 70.5] (p=0.016 compared with immunocompromised group, p=0.0096 compared with immunocompetent group). Conclusion: Among patients with bacterial pneumonia, BALF neutrophil percentage was not significantly decreased by a spectrum of immunocompromise. However, the subset of patients who were acutely neutropenic at the time of BAL sampling had significantly lower BALF % neutrophils. A traditional approach using BALF<50% to suggest against bacterial pneumonia may be inaccurate in this particular population.

An observational cohort study of bronchoalveolar lavage fluid galactomannan and Aspergillus culture positivity in patients requiring mechanical ventilation.

Rationale: Critically ill patients who develop invasive pulmonary aspergillosis (IPA) have high mortality rates despite antifungal therapy. Diagnosis is difficult in these patients. Bronchoalveolar lavage (BAL) fluid galactomannan (GM) is a helpful marker of infection, although the optimal cutoff for IPA is unclear. We aimed to evaluate the BAL fluid GM and fungal culture results, demographics, and outcomes among a large cohort of mechanically ventilated patients with suspected pneumonia. Methods: A single-center cohort study of patients enrolled in the Successful Clinical Response in Pneumonia Therapy (SCRIPT) study from June 2018 to March 2023. Demographics, BAL results, and outcomes data were extracted from the electronic health record and compared between groups of patients who grew Aspergillus on a BAL fluid culture, those who had elevated BAL fluid GM levels (defined as >0.5 or >0.8) but did not grow Aspergillus on BAL fluid culture, and those with neither. Results: Of over 1700 BAL samples from 688 patients, only 18 BAL samples grew Aspergillus. Patients who had a BAL sample grow Aspergillus (n=15) were older (median 71 vs 62 years, p=0.023), had more days intubated (29 vs 11, p=0.002), and more ICU days (34 vs 15, p=0.002) than patients whose BAL fluid culture was negative for Aspergillus (n=672). The BAL fluid galactomannan level was higher from samples that grew Aspergillus on culture than those that did not (median ODI 7.08 vs 0.11, p<0.001), though the elevation of BAL fluid GM varied across BAL samples for patients who had serial sampling. Patients who grew Aspergillus had a similar proportion of underlying immunocompromise compared with the patients who did not, and while no statistically significant difference in overall unfavorable outcome, had longer duration of ventilation and longer ICU stays. Conclusions: In this large cohort of critically ill patients with a high number of BAL samples with GM levels, we found a relatively low rate of Aspergillus growth. Patients who eventually grew Aspergillus had inconsistently elevated BAL fluid GM, and many patients with elevated BAL fluid GM did not grow Aspergillus. These data suggest that the pre-test probability of invasive pulmonary aspergillosis should be considered low in a general ICU population undergoing BAL evaluation to define the etiology of pneumonia. Improved scoring systems are needed to enhance pre-test probability for diagnostic test stewardship purposes.

Microbiology of Severe Community-Acquired Pneumonia and the Role of Rapid Molecular Techniques.

The microbiology of severe community acquired pneumonia (SCAP) has implications on management, clinical outcomes and public health policy. Therefore, knowledge of the etiologies of SCAP and methods to identify these microorganisms is key. Bacteria including Streptococcus pneumoniae, Staphylococcus aureus and Enterobacteriaceae continue to be important causes of SCAP. Viruses remain the most commonly identified etiology of SCAP. Atypical organisms are also important etiologies of SCAP and are critical to identify for public health. With the increased number of immunocompromised individuals, less common pathogens may also be found as the causative agent of SCAP. Traditional diagnostic tests, including semi-quantitative respiratory cultures, blood cultures and urinary antigens continue to hold an important role in the evaluation of patients with SCAP. Many of the limitations of the aforementioned tests are addressed by rapid, molecular diagnostic tests. Molecular diagnostics utilize culture-independent technology to identify species-specific genetic sequences. These tests are often semi-automated and provide results within hours, which provides an opportunity for expedient antibiotic stewardship. The existing literature suggests molecular diagnostic techniques may improve antibiotic stewardship in CAP, and future research should investigate optimal methods for implementation of these assays into clinical practice.

An exploratory survey about using ChatGPT in education, healthcare, and research.

OBJECTIVE: ChatGPT is the first large language model (LLM) to reach a large, mainstream audience. Its rapid adoption and exploration by the population at large has sparked a wide range of discussions regarding its acceptable and optimal integration in different areas. In a hybrid (virtual and in-person) panel discussion event, we examined various perspectives regarding the use of ChatGPT in education, research, and healthcare. MATERIALS AND METHODS: We surveyed in-person and online attendees using an audience interaction platform (Slido). We quantitatively analyzed received responses on questions about the use of ChatGPT in various contexts. We compared pairwise categorical groups with a Fisher's Exact. Furthermore, we used qualitative methods to analyze and code discussions. RESULTS: We received 420 responses from an estimated 844 participants (response rate 49.7%). Only 40% of the audience had tried ChatGPT. More trainees had tried ChatGPT compared with faculty. Those who had used ChatGPT were more interested in using it in a wider range of contexts going forwards. Of the three discussed contexts, the greatest uncertainty was shown about using ChatGPT in education. Pros and cons were raised during discussion for the use of this technology in education, research, and healthcare. DISCUSSION: There was a range of perspectives around the uses of ChatGPT in education, research, and healthcare, with still much uncertainty around its acceptability and optimal uses. There were different perspectives from respondents of different roles (trainee vs faculty vs staff). More discussion is needed to explore perceptions around the use of LLMs such as ChatGPT in vital sectors such as education, healthcare and research. Given involved risks and unforeseen challenges, taking a thoughtful and measured approach in adoption would reduce the likelihood of harm.

An Adjudication Protocol for Severe Pneumonia.

Background: Clinical end points that constitute successful treatment in severe pneumonia are difficult to ascertain and vulnerable to bias. The utility of a protocolized adjudication procedure to determine meaningful end points in severe pneumonia has not been well described. Methods: This was a single-center prospective cohort study of patients with severe pneumonia admitted to the medical intensive care unit. The objective was to develop an adjudication protocol for severe bacterial and/or viral pneumonia. Each episode of pneumonia was independently reviewed by 2 pulmonary and critical care physicians. If a discrepancy occurred between the 2 adjudicators, a third adjudicator reviewed the case. If a discrepancy remained after all 3 adjudications, consensus was achieved through committee review. Results: Evaluation of 784 pneumonia episodes during 593 hospitalizations achieved only 48.1% interobserver agreement between the first 2 adjudicators and 78.8% when agreement was defined as concordance between 2 of 3 adjudicators. Multiple episodes of pneumonia and presence of bacterial/viral coinfection in the initial pneumonia episode were associated with lower interobserver agreement. For an initial episode of bacterial pneumonia, patients with an adjudicated day 7-8 clinical impression of cure (compared with alternative impressions) were more likely to be discharged alive (odds ratio, 6.3; 95% CI, 3.5-11.6). Conclusions: A comprehensive adjudication protocol to identify clinical end points in severe pneumonia resulted in only moderate interobserver agreement. An adjudicated end point of clinical cure by day 7-8 was associated with more favorable hospital discharge dispositions, suggesting that clinical cure by day 7-8 may be a valid end point to use in adjudication protocols.

An exploratory survey about using ChatGPT in education, healthcare, and research.

Objective ChatGPT is the first large language model (LLM) to reach a large, mainstream audience. Its rapid adoption and exploration by the population at large has sparked a wide range of discussions regarding its acceptable and optimal integration in different areas. In a hybrid (virtual and in-person) panel discussion event, we examined various perspectives regarding the use of ChatGPT in education, research, and healthcare. Materials and Methods We surveyed in-person and online attendees using an audience interaction platform (Slido). We quantitatively analyzed received responses on questions about the use of ChatGPT in various contexts. We compared pairwise categorical groups with Fisher's Exact. Furthermore, we used qualitative methods to analyze and code discussions. Results We received 420 responses from an estimated 844 participants (response rate 49.7%). Only 40% of the audience had tried ChatGPT. More trainees had tried ChatGPT compared with faculty. Those who had used ChatGPT were more interested in using it in a wider range of contexts going forwards. Of the three discussed contexts, the greatest uncertainty was shown about using ChatGPT in education. Pros and cons were raised during discussion for the use of this technology in education, research, and healthcare. Discussion There was a range of perspectives around the uses of ChatGPT in education, research, and healthcare, with still much uncertainty around its acceptability and optimal uses. There were different perspectives from respondents of different roles (trainee vs faculty vs staff). More discussion is needed to explore perceptions around the use of LLMs such as ChatGPT in vital sectors such as education, healthcare and research. Given involved risks and unforeseen challenges, taking a thoughtful and measured approach in adoption would reduce the likelihood of harm.

Machine learning links unresolving secondary pneumonia to mortality in patients with severe pneumonia, including COVID-19.

BACKGROUNDDespite guidelines promoting the prevention and aggressive treatment of ventilator-associated pneumonia (VAP), the importance of VAP as a driver of outcomes in mechanically ventilated patients, including patients with severe COVID-19, remains unclear. We aimed to determine the contribution of unsuccessful treatment of VAP to mortality for patients with severe pneumonia.METHODSWe performed a single-center, prospective cohort study of 585 mechanically ventilated patients with severe pneumonia and respiratory failure, 190 of whom had COVID-19, who underwent at least 1 bronchoalveolar lavage. A panel of intensive care unit (ICU) physicians adjudicated the pneumonia episodes and endpoints on the basis of clinical and microbiological data. Given the relatively long ICU length of stay (LOS) among patients with COVID-19, we developed a machine-learning approach called CarpeDiem, which grouped similar ICU patient-days into clinical states based on electronic health record data.RESULTSCarpeDiem revealed that the long ICU LOS among patients with COVID-19 was attributable to long stays in clinical states characterized primarily by respiratory failure. While VAP was not associated with mortality overall, the mortality rate was higher for patients with 1 episode of unsuccessfully treated VAP compared with those with successfully treated VAP (76.4% versus 17.6%, P < 0.001). For all patients, including those with COVID-19, CarpeDiem demonstrated that unresolving VAP was associated with a transitions to clinical states associated with higher mortality.CONCLUSIONSUnsuccessful treatment of VAP is associated with higher mortality. The relatively long LOS for patients with COVID-19 was primarily due to prolonged respiratory failure, placing them at higher risk of VAP.FUNDINGNational Institute of Allergy and Infectious Diseases (NIAID), NIH grant U19AI135964; National Heart, Lung, and Blood Institute (NHLBI), NIH grants R01HL147575, R01HL149883, R01HL153122, R01HL153312, R01HL154686, R01HL158139, P01HL071643, and P01HL154998; National Heart, Lung, and Blood Institute (NHLBI), NIH training grants T32HL076139 and F32HL162377; National Institute on Aging (NIA), NIH grants K99AG068544, R21AG075423, and P01AG049665; National Library of Medicine (NLM), NIH grant R01LM013337; National Center for Advancing Translational Sciences (NCATS), NIH grant U01TR003528; Veterans Affairs grant I01CX001777; Chicago Biomedical Consortium grant; Northwestern University Dixon Translational Science Award; Simpson Querrey Lung Institute for Translational Science (SQLIFTS); Canning Thoracic Institute of Northwestern Medicine.

Comparing scientific abstracts generated by ChatGPT to real abstracts with detectors and blinded human reviewers.

Large language models such as ChatGPT can produce increasingly realistic text, with unknown information on the accuracy and integrity of using these models in scientific writing. We gathered fifth research abstracts from five high-impact factor medical journals and asked ChatGPT to generate research abstracts based on their titles and journals. Most generated abstracts were detected using an AI output detector, 'GPT-2 Output Detector', with % 'fake' scores (higher meaning more likely to be generated) of median [interquartile range] of 99.98% 'fake' [12.73%, 99.98%] compared with median 0.02% [IQR 0.02%, 0.09%] for the original abstracts. The AUROC of the AI output detector was 0.94. Generated abstracts scored lower than original abstracts when run through a plagiarism detector website and iThenticate (higher scores meaning more matching text found). When given a mixture of original and general abstracts, blinded human reviewers correctly identified 68% of generated abstracts as being generated by ChatGPT, but incorrectly identified 14% of original abstracts as being generated. Reviewers indicated that it was surprisingly difficult to differentiate between the two, though abstracts they suspected were generated were vaguer and more formulaic. ChatGPT writes believable scientific abstracts, though with completely generated data. Depending on publisher-specific guidelines, AI output detectors may serve as an editorial tool to help maintain scientific standards. The boundaries of ethical and acceptable use of large language models to help scientific writing are still being discussed, and different journals and conferences are adopting varying policies.

Clinical Features of COVID-19 and Differentiation from Other Causes of CAP.

Community-acquired pneumonia (CAP) is a significant cause of morbidity and mortality, one of the most common reasons for infection-related death worldwide. Causes of CAP include numerous viral, bacterial, and fungal pathogens, though frequently no specific organism is found. Beginning in 2019, the COVID-19 pandemic has caused incredible morbidity and mortality. COVID-19 has many features typical of CAP such as fever, respiratory distress, and cough, and can be difficult to distinguish from other types of CAP. Here, we highlight unique clinical features of COVID-19 pneumonia such as olfactory and gustatory dysfunction, lymphopenia, and distinct imaging appearance.

Obesity Is Associated with Attenuated Tissue Immunity in COVID-19.

Rationale: Obesity affects 40% of U.S. adults, is associated with a proinflammatory state, and presents a significant risk factor for the development of severe coronavirus disease (COVID-19). To date, there is limited information on how obesity might affect immune cell responses in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Objectives: To determine the impact of obesity on respiratory tract immunity in COVID-19 across the human lifespan. Methods: We analyzed single-cell transcriptomes from BAL in three ventilated adult cohorts with (n = 24) or without (n = 9) COVID-19 from nasal immune cells in children with (n = 14) or without (n = 19) COVID-19, and from peripheral blood mononuclear cells in an independent adult COVID-19 cohort (n = 42), comparing obese and nonobese subjects. Measurements and Main Results: Surprisingly, we found that obese adult subjects had attenuated lung immune or inflammatory responses in SARS-CoV-2 infection, with decreased expression of IFN-α, IFN-γ, and TNF-α (tumor necrosis factor α) response gene signatures in almost all lung epithelial and immune cell subsets, and lower expression of IFNG and TNF in specific lung immune cells. Peripheral blood immune cells in an independent adult cohort showed a similar but less marked reduction in type-I IFN and IFNγ response genes, as well as decreased serum IFNα, in obese patients with SARS-CoV-2. Nasal immune cells from obese children with COVID-19 also showed reduced enrichment of IFN-α and IFN-γ response genes. Conclusions: These findings show blunted tissue immune responses in obese patients with COVID-19, with implications for treatment stratification, supporting the specific application of inhaled recombinant type-I IFNs in this vulnerable subset.

Outcomes of Percutaneous Tracheostomy for Patients With SARS-CoV-2 Respiratory Failure.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause severe respiratory failure leading to prolonged mechanical ventilation. Data are just emerging about the practice and outcomes of tracheostomy in these patients. We reviewed our experience with tracheostomies for SARS-CoV-2. METHODS: We retrospectively reviewed the demographics, comorbidities, timing of mechanical ventilation, tracheostomy, and intensive care unit and hospital lengths of stay in SARS-CoV-2 patients who received tracheostomies performed by the interventional pulmonary team. A tertiary care, teaching hospital in Chicago, Illinois. From March 2020 to April 2021, our center had 473 patients intubated for SARS-CoV-2, and 72 (15%) had percutaneous bedside tracheostomy performed by the interventional pulmonary team. RESULTS: Median time from intubation to tracheostomy was 20 (interquartile range: 16 to 25) days. Demographics and comorbidities were similar between early and late tracheostomy, but early tracheostomy was associated with shorter intensive care unit lengths of stay and a shorter total duration of ventilation. To date, 39 (54%) patients have been decannulated, 17 (24%) before hospital discharge; median time to decannulation was 22 (IQR: 18 to 36) days. Patients that were decannulated were younger (56 vs. 69 y). The rate of decannulation for survivors was 82%. No providers developed symptoms or tested positive for SARS-CoV-2. CONCLUSION: Tracheostomy enhances care for patients with prolonged respiratory failure from SARS-CoV-2 since early tracheostomy is associated with shorter duration of critical care, and decannulation rates are high for survivors. It furthermore appears safe for both patients and operators.

A distinctive evolution of alveolar T cell responses is associated with clinical outcomes in unvaccinated patients with SARS-CoV-2 pneumonia.

Pathogen clearance and resolution of inflammation in patients with pneumonia require an effective local T cell response. Nevertheless, local T cell activation may drive lung injury, particularly during prolonged episodes of respiratory failure characteristic of severe SARS-CoV-2 pneumonia. While T cell responses in the peripheral blood are well described, the evolution of T cell phenotypes and molecular signatures in the distal lung of patients with severe pneumonia caused by SARS-CoV-2 or other pathogens is understudied. Accordingly, we serially obtained 432 bronchoalveolar lavage fluid samples from 273 patients with severe pneumonia and respiratory failure, including 74 unvaccinated patients with COVID-19, and performed flow cytometry, transcriptional, and T cell receptor profiling on sorted CD8+ and CD4+ T cell subsets. In patients with COVID-19 but not pneumonia secondary to other pathogens, we found that early and persistent enrichment in CD8+ and CD4+ T cell subsets correlated with survival to hospital discharge. Activation of interferon signaling pathways early after intubation for COVID-19 was associated with favorable outcomes, while activation of NF-κB-driven programs late in disease was associated with poor outcomes. Patients with SARS-CoV-2 pneumonia whose alveolar T cells preferentially targeted the Spike and Nucleocapsid proteins tended to experience more favorable outcomes than patients whose T cells predominantly targeted the ORF1ab polyprotein complex. These results suggest that in patients with severe SARS-CoV-2 pneumonia, alveolar T cell interferon responses targeting structural SARS-CoV-2 proteins characterize patients who recover, yet these responses progress to NF-κB activation against non-structural proteins in patients who go on to experience poor clinical outcomes.

Gearing up for battle: Harnessing adaptive T cell immunity against gram-negative pneumonia.

Pneumonia is one of the leading causes of morbidity and mortality worldwide and Gram-negative bacteria are a major cause of severe pneumonia. Despite advances in diagnosis and treatment, the rise of multidrug-resistant organisms and hypervirulent strains demonstrates that there will continue to be challenges with traditional treatment strategies using antibiotics. Hence, an alternative approach is to focus on the disease tolerance components that mediate immune resistance and enhance tissue resilience. Adaptive immunity plays a pivotal role in modulating these processes, thus affecting the incidence and severity of pneumonia. In this review, we focus on the adaptive T cell responses to pneumonia induced by Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. We highlight key factors in these responses that have potential for therapeutic targeting, as well as the gaps in current knowledge to be focused on in future work.

Comparison of traditional instruction versus nontraditional learning to improve trainee knowledge of urine culture practices in catheterized patients.

We surveyed trainees about their urine culture practices and assessed the impact of an educational intervention delivered electronically and in-person. Trainee scores improved across all levels of training and across all questions on the post-intervention survey, but there was no difference in scores by mode of education (P=0.91).

Anthropomorphic Character Animations Versus Digital Chalk Talks in a Resident Diabetes Pharmacotherapy Curriculum: a Randomized Controlled Trial.

BACKGROUND: Animation in medical education has boomed over the past two decades, and demand for distance learning technologies will likely continue in the context of the COVID-19 pandemic. However, experimental data guiding best practices for animation in medical education are scarce. OBJECTIVE: To compare the efficacy of two animated video styles in a diabetes pharmacotherapy curriculum for internal medicine residents. DESIGN: Learners were randomized to receive one of two versions of the same multimodal didactic curriculum. They received identical lectures, group activities, and quizzes, but were randomized to either digital chalk talk (DCT) videos or Sugar-Coated Science (SCS). SCS is an animated series using anthropomorphic characters, stories, and mnemonics to communicate knowledge. PARTICIPANTS: Ninety-two internal medicine residents at a single academic medical center received the curriculum within ambulatory medicine didactics. MAIN MEASURES: Knowledge was measured at multiple time points, as was residents' self-reported comfort using each medication class covered. Surveys assessed video acceptability and telepresence. Key themes were identified from open-ended feedback. KEY RESULTS: Baseline knowledge was low, consistent with prior needs assessments. On immediate posttest, mean scores were higher with SCS than DCT (74.8% versus 68.4%), but the difference was not statistically significant, p = 0.10. Subgroup analyses revealed increased knowledge in the SCS group for specific medication classes. Delayed posttest showed significant knowledge gains averaging 17.6% across all participants (p < 0.05); these gains were similar between animation types. SCS achieved significantly higher telepresence, entertainment, and acceptability scores than DCT. Qualitative data suggested that residents prioritize well-designed, multimodal curricula over specific animation characteristics. CONCLUSION: SCS and DCTs both led to learning within a multimodal curriculum, but SCS significantly enhanced learner experience. Animation techniques exemplified by both SCS and DCTs have roles in the medical educator toolkit. Selection between them should incorporate context, learner factors, and production resources.

Mathematical models to study the biology of pathogens and the infectious diseases they cause.

Mathematical models have many applications in infectious diseases: epidemiologists use them to forecast outbreaks and design containment strategies; systems biologists use them to study complex processes sustaining pathogens, from the metabolic networks empowering microbial cells to ecological networks in the microbiome that protects its host. Here, we (1) review important models relevant to infectious diseases, (2) draw parallels among models ranging widely in scale. We end by discussing a minimal set of information for a model to promote its use by others and to enable predictions that help us better fight pathogens and the diseases they cause.

Local and systemic responses to SARS-CoV-2 infection in children and adults.

It is not fully understood why COVID-19 is typically milder in children1-3. Here, to examine the differences between children and adults in their response to SARS-CoV-2 infection, we analysed paediatric and adult patients with COVID-19 as well as healthy control individuals (total n = 93) using single-cell multi-omic profiling of matched nasal, tracheal, bronchial and blood samples. In the airways of healthy paediatric individuals, we observed cells that were already in an interferon-activated state, which after SARS-CoV-2 infection was further induced especially in airway immune cells. We postulate that higher paediatric innate interferon responses restrict viral replication and disease progression. The systemic response in children was characterized by increases in naive lymphocytes and a depletion of natural killer cells, whereas, in adults, cytotoxic T cells and interferon-stimulated subpopulations were significantly increased. We provide evidence that dendritic cells initiate interferon signalling in early infection, and identify epithelial cell states associated with COVID-19 and age. Our matching nasal and blood data show a strong interferon response in the airways with the induction of systemic interferon-stimulated populations, which were substantially reduced in paediatric patients. Together, we provide several mechanisms that explain the milder clinical syndrome observed in children.

Prominent rash and multisystem inflammatory syndrome in a 29-year-old patient with COVID-19: a case report.

BACKGROUND: Adult patients with coronavirus disease present primarily with respiratory symptoms, but children and some adults may display a more systemic inflammatory syndrome with rash, fever, mucosal changes, and elevated inflammatory biomarkers. CASE PRESENTATION: Here, we report the case of a 29-year-old Hispanic patient presenting with significant rash and multisystem inflammation. We describe his clinical course, review dermatological manifestations of coronavirus disease, and summarize the pathophysiology of coronavirus disease-associated multisystem inflammation. CONCLUSION: This case should alert physicians to the atypical nature of presenting rash with minimal respiratory symptoms in coronavirus disease.

Bacterial Superinfection Pneumonia in Patients Mechanically Ventilated for COVID-19 Pneumonia.

Rationale: Current guidelines recommend patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia receive empirical antibiotics for suspected bacterial superinfection on the basis of weak evidence. Rates of ventilator-associated pneumonia (VAP) in clinical trials of patients with SARS-CoV-2 pneumonia are unexpectedly low. Objectives: We conducted an observational single-center study to determine the prevalence and etiology of bacterial superinfection at the time of initial intubation and the incidence and etiology of subsequent bacterial VAP in patients with severe SARS-CoV-2 pneumonia. Methods: Bronchoscopic BAL fluid samples from all patients with SARS-CoV-2 pneumonia requiring mechanical ventilation were analyzed using quantitative cultures and a multiplex PCR panel. Actual antibiotic use was compared with guideline-recommended therapy. Measurements and Main Results: We analyzed 386 BAL samples from 179 patients with SARS-CoV-2 pneumonia requiring mechanical ventilation. Bacterial superinfection within 48 hours of intubation was detected in 21% of patients. Seventy-two patients (44.4%) developed at least one VAP episode (VAP incidence rate = 45.2/1,000 ventilator days); 15 (20.8%) initial VAPs were caused by difficult-to-treat pathogens. The clinical criteria did not distinguish between patients with or without bacterial superinfection. BAL-based management was associated with significantly reduced antibiotic use compared with guideline recommendations. Conclusions: In patients with SARS-CoV-2 pneumonia requiring mechanical ventilation, bacterial superinfection at the time of intubation occurs in <25% of patients. Guideline-based empirical antibiotic management at the time of intubation results in antibiotic overuse. Bacterial VAP developed in 44% of patients and could not be accurately identified in the absence of microbiologic analysis of BAL fluid.