The local and systemic response to SARS-CoV-2 infection in children and adults

T1 Figure 1ConclusionsOverall, this largest paediatric single cell COVID-19 study to date showed significant differences in response to SARS-CoV-2 between children and adults, reflecting the changes of the immune landscape over developmental time, which in children are dominated by naïve and innate responses.

The assessment of bronchoalveolar lavage (BAL) fluid composition in critically ill patients with and without COVID-19 and AKI

Background: Recent reports identified enrichment of T cells and monocytes in the BAL fluid of patients with COVID-19 pneumonia, in contrast to neutrophilia in patients with non-COVID-19 pneumonia, which suggests a distinct immunopathology. We evaluated whether AKI, an independent risk factor for adverse outcomes, modifies BAL cell composition in critically ill patients. Methods: We retrospectively analyzed BAL specimens from 710 critically ill patients undergoing evaluation for pneumonia at an academic medical center from 3/2018-11/2020. Kruskal-Wallis tests compared distributions of BAL fluid % cell counts by COVID-19 and AKI status. Multivariable linear regression models tested the associations of COVID-19 status with the BAL fluid % cell counts. We tested for effect modification by AKI status. AKI was defined by the KDIGO criteria. Results: Mean age was 60±15 years and median baseline serum creatinine was 0.8 [0.6-1.1] mg/dl. COVID-19 was positive in 34.5% and AKI occurred in 42.8% of patients. Figure 1A shows differences in BAL fluid cell composition by COVID-19 and AKI status. Highest % of neutrophils were in COVID-19(-) AKI(-) patients and lowest in COVID-19(+) AKI(-) patients. Macrophages, monocytes, and lymphocytes were highest in COVID-19(+) AKI(-) patients and lowest in COVID-19(-) AKI(-) patients. COVID-19(+) patients had a significantly lower % of neutrophils and a higher % of monocytes and lymphocytes after multivariable adjustment (Figure 1B). Patients who were AKI(+) had decreased % of neutrophils when COVID-19(-), while the opposite effect was noted for COVID-19(+) (P for interaction=0.007). Conclusions: AKI may differentially modify the cell BAL fluid cell composition among patients with suspected pneumonia based on their COVID-19 status.

Nucleic Acid-based Testing for Noninfluenza Viral Pathogens in Adults with Suspected Community-acquired Pneumonia. An Official American Thoracic Society Clinical Practice Guideline

Background: This document provides evidence-based clinical practice guidelines on the diagnostic utility of nucleic acid-based testing of respiratory samples for viral pathogens other than influenza in adults with suspected community-acquired pneumonia (CAP). Methods: A multidisciplinary panel developed a Population-Intervention-Comparison-Outcome question, conducted a pragmatic systematic review, and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations.

Aspergillus superinfection and bronchoalveolar lavage galactomannan among patients with severe COVID-19-related respiratory failure

Rationale: The frequency of superinfection with Aspergillus among patients with severe COVID-19-related respiratory failure is unknown. The association of bronchoalveolar lavage (BAL) fluid markers, such as galactomannan, with the presence of Aspergillus infections is also unclear. Methods: Our cohort included all patients with COVID-19 admitted to the Northwestern Memorial Hospital ICU from March to November 2020 who were intubated and underwent a BAL;patients were identified as having COVID-19 by the presence of a flag in the electronic medical record. We evaluated BAL fluid data for fungal organisms and markers. Data analysis was performed in Excel and Prism, with non-parametric values compared by two-tailed Mann Whitney tests. Results: We identified 274 patients meeting study entry criteria. The median (interquartile range) age was 62 years (47-69), and 93 (34%) were female. 714 BALs were performed on these patients, and 457 galactomannan tests were sent from these BALs. Only six (2.2%) patients grew Aspergillus on BAL fluid culture;one patient never grew Aspergillus but given his significantly elevated BAL galactomannan of 7.81, was empirically treated. The median (IQR) optical density index of galactomannan for the BAL samples that grew Aspergillus was 6.69 (3.37-8.87) compared with 0.08 (0.06-0.13) for those that did not, p<0.001. Using our lab's reported galactomannan index cutoff of >0.5 as positive, with patients who grew Aspergillus on culture as gold standard, the test sensitivity was 91.7% and specificity was 94.6%;using the ATS recommended cutoff of >1.0 as positive, the sensitivity was 75.0% and specificity was 97.5%. The median (IQR) age of patients who grew Aspergillus was 71.5 years (64-80.5) (p=0.02 compared with the overall cohort). Only two were immunocompromised (diffuse large B-cell lymphoma and another was status post liver transplant). Of note, two patients who grew Aspergillus had visible mold or plaque seen during bronchoscopy;three had cavitary findings on imaging;three died. Conclusions: Aspergillus superinfection is uncommon among ventilated patients with COVID-19 but can occur in patients without typical immunocompromising risk factors. BAL fluid galactomannan levels are lower in patients without Aspergillus, and had reasonable specificity especially if cutoff of >1.0 was used. Future analysis should focus on additional factors that differentiate between these two groups.

Comparing ecmo characteristics and outcomes among COVID-19 and non-COVID-19 patients at a tertiary academic medical center

Rationale: Coronavirus disease 2019 (COVID-19) can cause severe respiratory failure that worsens despite maximal medical management. When to initiate extracorporeal membrane oxygenation (ECMO) and how to manage these patients on ECMO is not clear. Here, we present our experience with venovenous ECMO to support patients with COVID-19 and compare it to historic patients supported with VV-ECMO for other causes of respiratory failure. Methods: Patients admitted to our tertiary academic medical center in 2019 and 2020 who received VV ECMO support were included in this retrospective chart review. We examined patients with and without COVID-19 infection. We placed COVID-19 patients on ECMO who failed supportive care with mechanical ventilation using a high PEEP low tidal volume strategy, prone positioning, and neuromuscular blockade. Data analysis were done in Excel and Prism. Non-parametric data were compared with unpaired, two-tailed Mann-Whitney tests. Results: ECMO was provided to 26 COVID-19 patients and 38 patients without COVID-19. Median (interquartile range) age of COVID-19 patients was 49.5 (40.5-56.25), compared with non-COVID-19 patients: 53.5 (30.5-60.25), p=0.28. COVID-19 patients had a significantly higher BMI: 32 (30.1-35.9) vs. 26.4 (23.6-29.4), p<0.001. There were 27% female COVID-19 patients compared with 37% female non-COVID patients (p=0.43). COVID-19 patients had similar PaO2:FiO2 ratios as non-COVID patients on day of cannulation: 74 (69-112) vs 78 (60-205), p=0.65. COVID-19 patients had longer ventilator duration pre-cannulation (not including time spent intubated at outside hospitals prior to transfer to our center)-1.9 (1.4-7.0) days vs 0.7 (-.2-1.0) days, p<0.001. COVID patients spent more days on ECMO compared with non-COVID patients: 20.7 (7.3-36.5) vs. 11.5 (3.8-26.8), p=0.14. Twelve (46%) of the COVID-19 ECMO patients died, compared with 9 (25%) of the non-COVID ECMO patients, p=0.10. Conclusions: In patients with severe SARS-CoV-2 pneumonia induced ARDS who fail maximal supportive therapy with mechanical ventilation, outcomes are similar or worse than patients historically receiving VV ECMO support for respiratory failure. These findings highlight the need to determine the optimal timing of ECMO initiation and management in patients with severe SARS-CoV-2 pneumonia.