Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients

Xiong, Yong; Liu, Yuan; Cao, Liu; Wang, Dehe; Guo, Ming; Jiang, Ao; Guo, Dong; Hu, Wenjia; Yang, Jiayi; Tang, Zhidong; Wu, Honglong; Lin, Yan; Zhang, Meiyuan; Zhang, Qi; Shī, Mǎng; Liu, Yingle; Zhou, Yu; Lan, Ke; Chen, Yu

doi:10.1080/22221751.2020.1747363

Cited by 1,089 publications

(1,140 citation statements)

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“…Although the underlying pulmonary pathophysiology remains incompletely understood, severe COVID19 infection is associated with a marked alveolar inflammatory cell infiltrate, together with a systemic cytokine storm response 6 . Several studies have also reported evidence of a COVID19‐associated coagulopathy 5,7,8 .…”

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confidence: 99%

COVID19 coagulopathy in Caucasian patients

et al. 2020

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HF and LT contributed equally to this study. SummaryAlthough the pathophysiology underlying severe COVID19 remains poorly understood, accumulating data suggest that a lung-centric coagulopathy may play an important role. Elevated D-dimer levels which correlated inversely with overall survival were recently reported in Chinese cohort studies. Critically however, ethnicity has major effects on thrombotic risk, with a 3-4-fold lower risk in Chinese compared to Caucasians and a significantly higher risk in African-Americans. In this study, we investigated COVID19 coagulopathy in Caucasian patients. Our findings confirm that severe COVID19 infection is associated with a significant coagulopathy that correlates with disease severity. Importantly however, Caucasian COVID19 patients on low molecular weight heparin thromboprophylaxis rarely develop overt disseminated intravascular coagulation (DIC). In rare COVID19 cases where DIC does develop, it tends to be restricted to late-stage disease. Collectively, these data suggest that the diffuse bilateral pulmonary inflammation observed in COVID19 is associated with a novel pulmonary-specific vasculopathy termed pulmonary intravascular coagulopathy (PIC) as distinct to DIC. Given that thrombotic risk is significantly impacted by race, coupled with the accumulating evidence that coagulopathy is important in COVID19 pathogenesis, our findings raise the intriguing possibility that pulmonary vasculopathy may contribute to the unexplained differences that are beginning to emerge highlighting racial susceptibility to COVID19 mortality.

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confidence: 99%

COVID19 coagulopathy in Caucasian patients

et al. 2020

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“…In particular, we evaluated cell differentials, cell activation by morphological features, and cytokines assessment on retrieved BAL uids. Among cytokines, we decided to focus our attention on IL6, a wellknown in ammatory cytokine that has been used as a marker of macrophages activation in the peripheral blood of COVID-19 affected patients [13]; IL8, a pro-in ammatory CXC chemokine that exerts speci c chemotactic and activating functions on neutrophils; and IL10, an anti-in ammatory and immunoregulatory cytokine, produced by several immune effectors, whose role in SARS-CoV-2 infected patients is still in debate [9,14].…”

Section: Discussionmentioning

confidence: 99%

“…Currently, limited data are available about alveolar in ammatory status in COVID-19 patients because of concerns in relation to using bronchoscopy to avoid aerosol generation. A transcriptomic analysis was conducted by Xiong et al on bronchoalveolar lavage (BAL) samples obtained from a small number of COVID-19 patients and measured the expression levels of cytokines and chemokines [9]. Another report comparing three patients with moderate COVID-19 and six patients with severe infection through a single-cell RNA sequencing (scRNA-seq) on BAL cells revealed aberrant macrophage activation and the formation of tissue-resident CD8 + T cell in the lung of mild symptom patients [10].…”

Section: Introductionmentioning

confidence: 99%

Broncho-alveolar inflammation in COVID-19 patients: a correlation with clinical outcome

Pandolfi

Tommaso

Frangipane

et al. 2020

Preprint

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Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly reached pandemic proportions. We conducted a prospective study to assess deep lung inflammatory status in patients with moderate to severe COVID-19. Methods Diagnostic bronchoalveolar lavage (BAL) was performed in 33 adult patients with SARS-CoV-2 infection by real-time PCR on nasopharyngeal swab admitted to the Intensive care unit (ICU) (n = 28) and to the Intermediate Medicine Ward (IMW) (n = 5). We analyze the differential cell count, ultrastructure of cells and Interleukin(IL)6, 8 and 10 levels. Results ICU patients showed a marked increase in neutrophils (72%, 60–81), lower lymphocyte (8%, 4–12) and macrophages fractions (17%, 11–27) compared to IMW patients (3%, 2–17, 15%, 6–26 and 74%, 58–90, respectively) (p < 0.01). Ultrastructural study from ICU patients showed viral-like particles in cytopathic mononuclear cells however extensive cytopathic damage in all cell lineages. Immunostaining with anti-viral capsid and spike antibodies specifically immunoreacted with BAL cells, mostly cytopathic ones. IL6 and IL8 were significantly higher in ICU patients than in IMW (IL6 p < 0.01, IL8 p < 0.0001), and also in patients who did not survive (IL6 p < 0.05, IL8 p = 0.05 vs. survivors). IL10 did not show a significant variation between groups. Dividing patients by treatment received, lower BAL concentrations of IL6 were found in patients treated with steroids as compared to those treated with tocilizumab (p < 0.1) or antivirals (p < 0.05). Conclusions Alveolitis, associated with COVID-19, is mainly sustained by innate effectors which showed features of extensive activation. The burden of pro-inflammatory cytokines IL6 and IL8 in the broncho-alveolar environment is associated with clinical outcome.

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“…There has also been some work on integrated multi-omics signatures. For example, meta-transcriptome sequencing was conducted on the bronchoalveolar lavage uid of SARS-CoV-2 infected patients 18 . Proteomic and metabolomic analyses of the serum from COVID-19 patients have also been investigated [19][20][21] .…”

Section: Introductionmentioning

confidence: 99%

The Trans-omics Landscape of COVID-19

Chen

Ding

et al. 2020

Preprint

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The outbreak of coronavirus disease 2019 (COVID-19) has been causing a global health emergency. Although previous studies investigated COVID-19 at different omics levels, the molecular hallmarks of COVID-19, especially in those patients without comorbidities, have not been fully investigated. Here, we presented a trans-omics landscape for COVID-19 based on integrative analysis of genomic, transcriptomic, proteomic, metabolomic and lipidomic profiles from blood samples of 231 COVID-19 patients, ranging from asymptomatic to critically ill, importantly excluding those with any comorbidities. Notably, we found neutrophils heterogeneity existed between asymptomatic and critically ill patients. Expression discordance of inflammatory cytokines at mRNA and protein levels in asymptomatic patients could possibly be explained by post-transcriptional regulation by RNA binding proteins (RBPs) and microRNAs. Neutrophils over-activation, induced arginine depletion, and tryptophan metabolites accumulation contributed to T/NK cell dysfunction in critical patients. Anti-virus interferons were gradually suppressed along with disease severity. Overall, our study systematically revealed multi-omics characteristics of COVID-19, and the data we generated could hopefully help illuminate COVID-19 pathogenesis and provide valuable clues about potential therapeutic strategies for COVID-19.

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Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients

Cited by 1,089 publications

References 54 publications

COVID19 coagulopathy in Caucasian patients

COVID19 coagulopathy in Caucasian patients

Broncho-alveolar inflammation in COVID-19 patients: a correlation with clinical outcome

The Trans-omics Landscape of COVID-19

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