Acute Respiratory Distress Syndrome due to Mycoplasma pneumoniae Misinterpreted as SARS-CoV-2 Infection

Background. In 2020, a novel coronavirus caused a global pandemic with a clinical picture termed COVID-19, accounting for numerous cases of ARDS. However, there are still other infectious causes of ARDS that should be considered, especially as the majority of these pathogens are specifically treatable. Case Presentation. We present the case of a 36-year-old gentleman who was admitted to the hospital with flu-like symptoms, after completing a half-marathon one week before admission. As infection with SARS-CoV-2 was suspected based on radiologic imaging, the hypoxemic patient was immediately transferred to the ICU, where he developed ARDS. Empiric antimicrobial chemotherapy was initiated, the patient deteriorated further, therapy was changed, and the patient was transferred to a tertiary care ARDS center. As cold agglutinins were present, the hypothesis of an infection with SARS-CoV-2 was then questioned. Bronchoscopic sampling revealed Mycoplasma (M.) pneumoniae. When antimicrobial chemotherapy was adjusted, the patient recovered quickly. Conclusion. Usually, M. pneumoniae causes mild disease. When antimicrobial chemotherapy was adjusted, the patient recovered quickly. The case underlines the importance to adhere to established treatment guidelines, scrutinize treatment modalities, and not to forget other potential causes of severe pneumonia or ARDS

Respiratory Physiology of COVID-19 and Influenza Associated Acute Respiratory Distress Syndrome

There is ongoing debate whether lung physiology of COVID-19-associated acute respiratory distress syndrome (ARDS) differs from ARDS of other origin. Objective: The aim of this study was to analyze and compare how critically ill patients with COVID-19 and Influenza A or B were ventilated in our tertiary care center with or without extracorporeal membrane oxygenation (ECMO). We ask if acute lung failure due to COVID-19 requires different intensive care management compared to conventional ARDS. Methods: 25 patients with COVID-19-associated ARDS were matched to a cohort of 25 Influenza patients treated in our center from 2011 to 2021. Subgroup analysis addressed whether patients on ECMO received different mechanical ventilation than patients without extracorporeal support. Results: Compared to Influenza-associated ARDS, COVID-19 patients had higher ventilatory system compliance (40.7 mL/mbar [31.8–46.7 mL/mbar] vs. 31.4 mL/mbar [13.7–42.8 mL/mbar], p = 0.198), higher ventilatory ratio (1.57 [1.31–1.84] vs. 0.91 [0.44–1.38], p = 0.006) and higher minute ventilation at the time of intubation (mean minute ventilation 10.7 L/min [7.2–12.2 L/min] for COVID-19 vs. 6.0 L/min [2.5–10.1 L/min] for Influenza, p = 0.013). There were no measurable differences in P/F ratio, positive end-expiratory pressure (PEEP) and driving pressures (∆P). Respiratory system compliance deteriorated considerably in COVID-19 patients on ECMO during 2 weeks of mechanical ventilation (Crs, mean decrease over 2 weeks −23.87 mL/mbar ± 32.94 mL/mbar, p = 0.037) but not in ventilated Influenza patients on ECMO and less so in ventilated COVID-19 patients without ECMO. For COVID-19 patients, low driving pressures on ECMO were strongly correlated to a decline in compliance after 2 weeks (Pearson’s R 0.80, p = 0.058). Overall mortality was insignificantly lower for COVID-19 patients compared to Influenza patients (40% vs. 48%, p = 0.31). Outcome was insignificantly worse for patients requiring veno-venous ECMO in both groups (50% mortality for COVID-19 on ECMO vs. 27% without ECMO, p = 0.30/56% vs. 34% mortality for Influenza A/B with and without ECMO, p = 0.31). Conclusion: The pathophysiology of early COVID-19-associated ARDS differs from Influenza-associated acute lung failure by sustained respiratory mechanics during the early phase of ventilation. We question whether intubated COVID-19 patients on ECMO benefit from extremely low driving pressures, as this appears to accelerate derecruitment and consecutive loss of ventilatory system compliance

Antibiotic therapeutic drug monitoring in intensive care patients treated with different modalities of extracorporeal membrane oxygenation (ECMO) and renal replacement therapy: a prospective, observational single-center study

Background: Efective antimicrobial treatment is key to reduce mortality associated with bacterial sepsis in patients on intensive care units (ICUs). Dose adjustments are often necessary to account for pathophysiological changes or renal replacement therapy. Extracorporeal membrane oxygenation (ECMO) is increasingly being used for the treatment of respiratory and/or cardiac failure. However, it remains unclear whether dose adjustments are necessary to avoid subtherapeutic drug levels in septic patients on ECMO support. Here, we aimed to evaluate and comparatively assess serum concentrations of continuously applied antibiotics in intensive care patients being treated with and without ECMO. Methods: Between October 2018 and December 2019, we prospectively enrolled patients on a pneumological ICU in southwest Germany who received antibiotic treatment with piperacillin/tazobactam, ceftazidime, meropenem, or linezolid. All antibiotics were applied using continuous infusion, and therapeutic drug monitoring of serum concentrations (expressed as mg/L) was carried out using high-performance liquid chromatography. Target concentrations were defned as fourfold above the minimal inhibitory concentration (MIC) of susceptible bacterial isolates, according to EUCAST breakpoints

Killer immunoglobulin-like receptor 2DS5 is associated with recovery from coronavirus disease 2019

Background Despite numerous advances in the identification of risk factors for the development of severe coronavirus disease 2019 (COVID-19), factors that promote recovery from COVID-19 remain unknown. Natural killer (NK) cells provide innate immune defense against viral infections and are known to be activated during moderate and severe COVID-19. Killer immunoglobulin-like receptors (KIR) mediate NK cell cytotoxicity through recognition of an altered MHC-I expression on infected target cells. However, the influence of KIR genotype on outcome of patients with COVID-19 has not been investigated so far. We retrospectively analyzed the outcome associations of NK cell count and KIR genotype of patients with COVID-19 related severe ARDS treated on our tertiary intensive care unit (ICU) between February and June 2020 and validated our findings in an independent validation cohort of patients with moderate COVID-19 admitted to our tertiary medical center. Results Median age of all patients in the discovery cohort (n = 16) was 61 years (range 50–71 years). All patients received invasive mechanical ventilation; 11 patients (68%) required extracorporeal membrane oxygenation (ECMO). Patients who recovered from COVID-19 had significantly higher median NK cell counts during the whole observational period compared to patients who died (121 cells/µL, range 16–602 cells/µL vs 81 cells/µL, range 6–227 cells/µL, p-value = 0.01). KIR2DS5 positivity was significantly associated with shorter time to recovery (21.6 ± 2.8 days vs. 44.6 ± 2.2 days, p-value = 0.01). KIR2DS5 positivity was significantly associated with freedom from transfer to ICU (0% vs 9%, p-value = 0.04) in the validation cohort which consisted of 65 patients with moderate COVID-19. Conclusion NK cells and KIR genotype might have an impact on recovery from COVID-19

Microbiological airway colonization in COPD patients with severe emphysema undergoing endoscopic lung volume reduction

Background: Endoscopic lung volume reduction (eLVR) is a therapeutic option for selected patients with COPD and severe emphysema. Infectious exacerbations are serious events in these vulnerable patients; hence, prophylactic antibiotics are often prescribed postinterventionally. However, data on the microbiological airway colonization at the time of eLVR are scarce, and there are no evidence-based recommendations regarding a rational antibiotic regimen. Objective: The aim of this study was to perform a clinical and microbiological analysis of COPD patients with advanced emphysema undergoing eLVR with endobronchial valves at a single German University hospital, 2012–2017. Patients and methods: Bronchial aspirates were obtained prior to eLVR and sent for microbiological analysis. Antimicrobial susceptibility testing of bacterial isolates was performed, and pathogen colonization was retrospectively compared with clinical parameters. Results: At least one potential pathogen was found in 47% (30/64) of patients. Overall, Gram-negative bacteria constituted the most frequently detected pathogens. The single most prevalent species were Haemophilus influenzae (9%), Streptococcus pneumoniae (6%), and Staphylococcus aureus (6%). No multidrug resistance was observed, and Pseudomonas aeruginosa occurred in <5% of samples. Patients without microbiological airway colonization showed more severe airflow limitation, hyperinflation, and chronic hypercapnia compared to those with detected pathogens. Conclusion: Microbiological airway colonization was frequent in patients undergoing eLVR but not directly associated with poorer functional status. Resistance testing results do not support the routine use of antipseudomonal antibiotics in these patients

TNF-related apoptosis-inducing ligand, interferon gamma-induced protein 10, and C-reactive protein in predicting the progression of SARS-CoV-2 infection : a prospective cohort study

Background: Early prognostication of COVID-19 severity will potentially improve patient care. Biomarkers, such as TNF-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein 10 (IP-10), and C-reactive protein (CRP), might represent possible tools for point-of-care testing and severity prediction. Methods: In this prospective cohort study, we analyzed serum levels of TRAIL, IP-10, and CRP in patients with COVID-19, compared them with control subjects, and investigated the association with disease sever ity. Results: A total of 899 measurements were performed in 132 patients (mean age 64 years, 40.2% females). Among patients with COVID-19, TRAIL levels were lower (49.5 vs 87 pg/ml, P = 0.0142), whereas IP-10 and CRP showed higher levels (667.5 vs 127 pg/ml, P <0.001; 75.3 vs 1.6 mg/l, P <0.001) than healthy controls. TRAIL yielded an inverse correlation with length of hospital and intensive care unit (ICU) stay, Simplified Acute Physiology Score II, and National Early Warning Score, and IP-10 showed a positive cor relation with disease severity. Multivariable regression revealed that obesity (adjusted odds ratio [aOR] 5.434, 95% confidence interval [CI] 1.005-29.38), CRP (aOR 1.014, 95% CI 1.002-1.027), and peak IP-10 (aOR 1.001, 95% CI 1.00-1.002) were independent predictors of in-ICU mortality

Invasion and Persistence of Infectious Agents in Fragmented Host Populations

One of the important questions in understanding infectious diseases and their prevention and control is how infectious agents can invade and become endemic in a host population. A ubiquitous feature of natural populations is that they are spatially fragmented, resulting in relatively homogeneous local populations inhabiting patches connected by the migration of hosts. Such fragmented population structures are studied extensively with metapopulation models. Being able to define and calculate an indicator for the success of invasion and persistence of an infectious agent is essential for obtaining general qualitative insights into infection dynamics, for the comparison of prevention and control scenarios, and for quantitative insights into specific systems. For homogeneous populations, the basic reproduction ratio plays this role. For metapopulations, defining such an ‘invasion indicator’ is not straightforward. Some indicators have been defined for specific situations, e.g., the household reproduction number . However, these existing indicators often fail to account for host demography and especially host migration. Here we show how to calculate a more broadly applicable indicator for the invasion and persistence of infectious agents in a host metapopulation of equally connected patches, for a wide range of possible epidemiological models. A strong feature of our method is that it explicitly accounts for host demography and host migration. Using a simple compartmental system as an example, we illustrate how can be calculated and expressed in terms of the key determinants of epidemiological dynamics