Dataset Information

Vascular neutrophilic inflammation and immunothrombosis distinguish severe COVID-19 from influenza pneumonia.

ABSTRACT:

Objective

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to severe pneumonia, but also thrombotic complications and non-pulmonary organ failure. Recent studies suggest intravascular neutrophil activation and subsequent immune cell-triggered immunothrombosis as a central pathomechanism linking the heterogenous clinical picture of coronavirus disease 2019 (COVID-19). We sought to study whether immunothrombosis is a pathognomonic factor in COVID-19 or a general feature of (viral) pneumonia, as well as to better understand its upstream regulation.

Approach and results

By comparing histopathological specimens of SARS-CoV-2 with influenza-affected lungs, we show that vascular neutrophil recruitment, NETosis, and subsequent immunothrombosis are typical features of severe COVID-19, but less prominent in influenza pneumonia. Activated neutrophils were typically found in physical association with monocytes. To explore this further, we combined clinical data of COVID-19 cases with comprehensive immune cell phenotyping and bronchoalveolar lavage fluid scRNA-seq data. We show that a HLADR^low CD9^low monocyte population expands in severe COVID-19, which releases neutrophil chemokines in the lungs, and might in turn explain neutrophil expansion and pulmonary recruitment in the late stages of severe COVID-19.

Conclusions

Our data underline an innate immune cell axis causing vascular inflammation and immunothrombosis in severe SARS-CoV-2 infection.

SUBMITTER: Nicolai L

PROVIDER: S-EPMC7753335 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Publications

Vascular neutrophilic inflammation and immunothrombosis distinguish severe COVID-19 from influenza pneumonia.

Nicolai Leo L Leunig Alexander A Brambs Sophia S Kaiser Rainer R Joppich Markus M Hoffknecht Marie-Louise ML Gold Christoph C Engel Anouk A Polewka Vivien V Muenchhoff Maximilian M Hellmuth Johannes C JC Ruhle Adrian A Ledderose Stephan S Weinberger Tobias T Schulz Heiko H Scherer Clemens C Rudelius Martina M Zoller Michael M Keppler Oliver T OT Zwißler Bernhard B von Bergwelt-Baildon Michael M Kääb Stefan S Zimmer Ralf R Bülow Roman D RD von Stillfried Saskia S von Stillfried Saskia S Boor Peter P Massberg Steffen S Pekayvaz Kami K Stark Konstantin K

Journal of thrombosis and haemostasis : JTH 20201220 2

<h4>Objective</h4>Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to severe pneumonia, but also thrombotic complications and non-pulmonary organ failure. Recent studies suggest intravascular neutrophil activation and subsequent immune cell-triggered immunothrombosis as a central pathomechanism linking the heterogenous clinical picture of coronavirus disease 2019 (COVID-19). We sought to study whether immunothrombosis is a pathognomonic factor in COVID-19 or a ...[more]

PMID: 33217134

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Project description:BackgroundRacial/ethnic minorities are at higher risk for severe COVID-19. This may be related to social determinants that lead to chronic inflammatory states. The aims of the study were to determine if there are racial/ethnic disparities with inflammatory markers and association of methylprednisolone to in hospital survival.MethodsThis was a secondary analysis of a retrospective cohort study of patients ≥ 18 years of age and admitted for severe COVID-19 pneumonia between March and June 2020 in 13 Hospitals in New Jersey, United States. Patients who received other formulation of corticosteroids were not included. Area under the receiver operating characteristics curves were performed to test for discriminatory ability of each inflammatory makers. Univariate and multivariate Cox regression assessed the association of variables to in hospital survival.ResultsPropensity matched sample (n = 759) between no methylprednisolone (n = 380) and methylprednisolone (n = 379) had 338 Whites, 102 Blacks, 61 Asian/Indians, and 251 non-Black non-White Hispanics. Compared to CRP, area under receiving operating characteristic curve for d-dimer in Hispanics (0.742) was statistically different (DeLong Test P = 0.0041). Multivariate cox regression showed that different variables in Blacks [age ≥ 60 years (HR = 3.71, P = 0.0281), mechanical ventilation (HR = 5.07, P = 0.0281) and creatinine ≥ 1.5 mg/dL (HR = 3.61, P = 0.0007)], Whites [cancer (HR = 1.68, P = 0.0213), qSOFA score of 1 (HR = 1.81, P = 0.0213), qSOFA score of 2 (HR = 5.16, P < 0.0001), qSOFA score of 3 (HR = 11.81, P < 0.0001) and creatinine ≥ 1.5 mg/dL (HR = 2.16, P = 0.0006)], Hispanics [hypertension (HR = 2.52, P = 0.0007), cancer (HR = 2.99, P = 0.0244 and D-dimer ≥ 2 mcg/mL (HR = 2.22, P = 0.0077)], and Asian/Indians [ chronic kidney disease (HR = 6.36, P = 0.0031) and CRP > 20 mg/L (HR = 5.02, P = 0.0032)] were statistically significant for mortality. Low dose and high dose methylprednisolone were significantly associated with prolonged survival in Whites [low dose (HR = 0.37, P < 0.0001) and high dose (HR = 0.48, P < 0.0183)] and Asian/Indians [low dose (HR = 0.13, P = 0.0101) and high dose (HR = 0.15, P = 0.01)]. However, high dose was not associated with improved survival compared to low dose. Methylprednisolone was not associated with prolonged survival in Blacks and Hispanics.ConclusionRacial/Ethnic disparities with inflammatory markers preclude the use of one marker as a predictor of survival. Methylprednisolone is associated with prolonged survival in Asian/Indians and Whites.

Project description:BackgroundSimilar to influenza, coinfections and superinfections are common and might result in poor prognosis. Our study aimed to compare the characteristics and risks of coinfections and superinfections in severe COVID-19 and influenza virus pneumonia.MethodsThe data of patients with COVID-19 and influenza admitted to the intensive care unit (ICU) were retrospectively analyzed. The primary outcome was to describe the prevalence and pathogenic distribution of coinfections/ICU-acquired superinfections in the study population. The secondary outcome was to evaluate the independent risk factors for coinfections/ICU-acquired superinfections at ICU admission. Multivariate analysis of survivors and non-survivors was performed to investigate whether coinfections/ICU-acquired superinfections was an independent prognostic factor.ResultsIn the COVID-19 (n = 123) and influenza (n = 145) cohorts, the incidence of coinfections/ICU-acquired superinfections was 33.3%/43.9 and 35.2%/52.4%, respectively. The most common bacteria identified in coinfection cases were Enterococcus faecium, Pseudomonas aeruginosa, and Acinetobacter baumannii (COVID-19 cohort) and A. baumannii, P. aeruginosa, and Klebsiella pneumoniae (influenza cohort). A significant higher proportion of coinfection events was sustained by Aspergillus spp. [(22/123, 17.9% in COVID-19) and (18/145, 12.4% in influenza)]. The COVID-19 group had more cases of ICU-acquired A. baumannii, Corynebacterium striatum and K. pneumoniae. A. baumannii, P. aeruginosa, and K. pneumoniae were the three most prevalent pathogens in the influenza cases with ICU-acquired superinfections. Patients with APACHE II ≥18, CD8+ T cells ≤90/μL, and 50 < age ≤ 70 years were more susceptible to coinfections; while those with CD8+ T cells ≤90/μL, CRP ≥120 mg/L, IL-8 ≥ 20 pg./mL, blood glucose ≥10 mmol/L, hypertension, and smoking might had a higher risk of ICU-acquired superinfections in the COVID-19 group. ICU-acquired superinfection, corticosteroid administration for COVID-19 treatment before ICU admission, and SOFA score ≥ 7 were independent prognostic factors in patients with COVID-19.ConclusionPatients with COVID-19 or influenza had a high incidence of coinfections and ICU-acquired superinfections. The represent agents of coinfection in ICU patients were different from those in the general ward. These high-risk patients should be closely monitored and empirically treated with effective antibiotics according to the pathogen.

Dataset Information

Vascular neutrophilic inflammation and immunothrombosis distinguish severe COVID-19 from influenza pneumonia.

Objective

Approach and results

Conclusions

Publications

Vascular neutrophilic inflammation and immunothrombosis distinguish severe COVID-19 from influenza pneumonia.

Similar Datasets

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