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

2020 ◽  
Author(s):  
Laura Pandolfi ◽  
Fossali Tommaso ◽  
Frangipane Vanessa ◽  
Bozzini Sara ◽  
Morosini Monica ◽  
...  

Abstract Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly reached pandemic proportions. Given that the main target of SARS-CoV-2 are lungs leading to severe pneumonia with hyperactivation of the inflammatory cascade, we conducted a prospective study to assess alveolar 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 (1.24 x 105 ml-1 , 0.85-2.07), lower lymphocyte (0.97 x 105 ml-1, 0.024-0.34) and macrophages fractions (0.43 x 105 ml-1, 0.34-1.62) compared to IMW patients (0.095 x 105 ml-1, 0.05-0.73; 0.47 x 105 ml-1, 0.28-1.01 and 2.14 x 105 ml-1, 1.17-3.01, respectively) (p<0.01). Ultrastructural study of ICU patients BAL showed viral-like particles in cytopathic mononuclear cells and an 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.

Author(s):  
Laura Pandolfi ◽  
Tommaso Fossali ◽  
Vanessa Frangipane ◽  
Sara Bozzini ◽  
Monica Morosini ◽  
...  

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. 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. 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). 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


2020 ◽  
Author(s):  
laura pandolfi ◽  
Fossali Tommaso ◽  
Frangipane Vanessa ◽  
Bozzini Sara ◽  
Morosini Monica ◽  
...  

Abstract 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.


2020 ◽  
Author(s):  
laura pandolfi ◽  
Fossali Tommaso ◽  
Frangipane Vanessa ◽  
Bozzini Sara ◽  
Morosini Monica ◽  
...  

Abstract Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly reached pandemic proportions. Given that the main target of SARS-CoV-2 are lungs leading to severe pneumonia with hyperactivation of the inflammatory cascade, we conducted a prospective study to assess alveolar 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 (1.24 x 105 ml-1 , 0.85-2.07), lower lymphocyte (0.97 x 105 ml-1, 0.024-0.34) and macrophages fractions (0.43 x 105 ml-1, 0.34-1.62) compared to IMW patients (0.095 x 105 ml-1, 0.05-0.73; 0.47 x 105 ml-1, 0.28-1.01 and 2.14 x 105 ml-1, 1.17-3.01, respectively) (p<0.01). Study of ICU patients BAL by electron transmission microscopy showed viral particles inside mononuclear cells confirmed by immunostaining with anti-viral capsid and spike antibodies. 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.


2020 ◽  
Author(s):  
Laura Pandolfi ◽  
Fossali Tommaso ◽  
Frangipane Vanessa ◽  
Bozzini Sara ◽  
Morosini Monica ◽  
...  

Abstract Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly reached pandemic proportions. Given that the main target of SARS-CoV-2 are lungs leading to severe pneumonia with hyperactivation of the inflammatory cascade, we conducted a prospective study to assess alveolar 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 (1.24 x 105 ml-1 , 0.85-2.07), lower lymphocyte (0.97 x 105 ml-1, 0.024-0.34) and macrophages fractions (0.43 x 105 ml-1, 0.34-1.62) compared to IMW patients (0.095 x 105 ml-1, 0.05-0.73; 0.47 x 105 ml-1, 0.28-1.01 and 2.14 x 105 ml-1, 1.17-3.01, respectively) (p<0.01). Study of ICU patients BAL by electron transmission microscopy showed viral particles inside mononuclear cells confirmed by immunostaining with anti-viral capsid and spike antibodies. 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.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Laura Pandolfi ◽  
Tommaso Fossali ◽  
Vanessa Frangipane ◽  
Sara Bozzini ◽  
Monica Morosini ◽  
...  

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly reached pandemic proportions. Given that the main target of SARS-CoV-2 are lungs leading to severe pneumonia with hyperactivation of the inflammatory cascade, we conducted a prospective study to assess alveolar 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 (1.24 × 105 ml− 1, 0.85–2.07), lower lymphocyte (0.97 × 105 ml− 1, 0.024–0.34) and macrophages fractions (0.43 × 105 ml− 1, 0.34–1.62) compared to IMW patients (0.095 × 105 ml− 1, 0.05–0.73; 0.47 × 105 ml− 1, 0.28–1.01 and 2.14 × 105 ml− 1, 1.17–3.01, respectively) (p < 0.01). Study of ICU patients BAL by electron transmission microscopy showed viral particles inside mononuclear cells confirmed by immunostaining with anti-viral capsid and spike antibodies. 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.


2020 ◽  
Author(s):  
laura pandolfi ◽  
Fossali Tommaso ◽  
Frangipane Vanessa ◽  
Bozzini Sara ◽  
Morosini Monica ◽  
...  

Abstract Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly reached pandemic proportions. Given that the main target of SARS-CoV-2 are lungs leading to severe pneumonia with hyperactivation of the inflammatory cascade, we conducted a prospective study to assess alveolar 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 (1.24 x 105 ml-1 , 0.85-2.07), lower lymphocyte (0.97 x 105 ml-1, 0.024-0.34) and macrophages fractions (0.43 x 105 ml-1, 0.34-1.62) compared to IMW patients (0.095 x 105 ml-1, 0.05-0.73; 0.47 x 105 ml-1, 0.28-1.01 and 2.14 x 105 ml-1, 1.17-3.01, respectively) (p<0.01). Study of ICU patients BAL by electron transmission microscopy showed viral particles inside mononuclear cells confirmed by immunostaining with anti-viral capsid and spike antibodies. 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.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 13-13
Author(s):  
Viola Maria Popov ◽  
Lelia Iliescu ◽  
Marius Ioan Balea ◽  
Daniela Georgeta Georgescu ◽  
Mihaela Andreescu ◽  
...  

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a highly infectious disease. The pathogenic mechanism of COVID-19 pneumonia involved excessive immune reaction in the host - a "cytokine storm", that determined extensive tissue damage associated with coagulation abnormalities. Severity of this disease is associated with comorbidities such as hypertension, obesity, pulmonary disease or age. Thrombotic complications are reported during COVID-19 evolution even with prophylaxis. OBJECTIVE: In this study, we evaluate hematological and coagulation parameters in order to obtain predictors for an unfavourable evolution of the patient. DESIGN AND SETTING: We performed a prospective study that included all patients admitted in our hospital in Hematology, Pneumology, and Intensive Care Unit (ICU) Department at Colentina Clinical Hospital during April - July 2020. The study group included 144 patients that were split into ICU and non-ICU patients. All patients were SARS-CoV-2-positive by molecular test. The distribution according to gender was as follows: 67 male with median age: 61 (min 22, max 88) and 77 female with median age: 57 (min 17, max 92). RESULTS: Age is an important risk factor for the severity; 50 patients admitted in ICU with median age 67 (min 34, max 92) and 94 non-ICU patients with median age 52.5 (min 17, max 92), p=0.00003. Associated comorbidities were important and were present in both groups. In ICU patients, we obtained lower level of lymphocytes compared with non ICU group median: 1 x 103/L (min 0.04 x 103/L max 3.28 x 103/L) vs 1.57 x 103/L (min 0.39 x 103/L max 23.35 x 103/L), p=0.0001. There are no significant differences between groups for the rest of hematological parameters. The neutrophil/lymphocytes ratio (NLR) is with statistical difference between ICU and non-ICU groups: 2.34 (min 1.06, max 31.90) vs 7.94 (min 2.18, max 90.04), p&lt;0.000001. This indicator seems to be predictor for severe evolution; a high correlation with IL-6 level (r=0.73, p&lt; 0.001) was obtained. NLR in association with IL-6, CRP and ferritin level are important factors in severe evolution of COVID-19 (severe pneumonia-more than 50% of lung evaluated by CT-scan and presence of any complications during COVID-19 evolution), coefficient of determination-R2 =0.69, R2 - adjusted 0.67, p&lt;0.0001). The ICU patients with unfavourable evolution had a higher level of D-Dimers at the admission in hospital compared with ICU patients who were discharged from the hospital (3.42 mg/ml FEU vs 1.09 mg/ml FEU, p=0.01). Patients with thrombosis (stroke, myocardial infarction, deep venous thrombosis, thromboembolism) during COVID-19 evolution have higher level of D Dimers compared with patients without thrombotic complications (7.35 mg/ml FEU vs 0.82 mg/ml FEU), p=0.0001. There are no difference for another coagulation tests (APTT, Quick time) or Protein C, Protein S and Antithrombin III level. CONCLUSIONS: We conclude that NLR in association with feritin, CRP and IL-6 assessment are important to be evaluated in COVID-19 patient in order to expect a severe evolution of the disease. D- Dimer should be an important parameter to be evaluated for all COVID-19 patients in order to identify COVID-19 patients with high risk of thrombotic complications. Disclosures No relevant conflicts of interest to declare.


1998 ◽  
Vol 11 (02) ◽  
pp. 76-79 ◽  
Author(s):  
B. M. Turner ◽  
R. H. Abercromby ◽  
J. Innes ◽  
W. M. McKee ◽  
M. G. Ness

SummaryA prospective study was made of 17 dogs with ununited anconeal process treated by osteotomy of the proximal ulna. The effect of the surgery on lameness was evaluated subjectively and the elbows were assessed radiographically for evidence of anconeal fusion and healing of the osteotomy. Whilst clinical outcome was generally good and complications infrequent, relatively few cases achieved anconeal fusion. These results do not compare well with the results of a previous study but this disparity may be due in part to differences in patient population and radiographic evaluation.Further work is required to establish how best to achieve predictable anconeal fusion.Proximal ulnar osteotomy was used to treat 17 dogs with ununited anconeal process. Clinical results were good but anconeal fusion was not achieved consistently. Further work is needed to determine how best to achieve predictable anconeal fusion.


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