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1.
Front Immunol ; 12: 708149, 2021.
Article in English | MEDLINE | ID: covidwho-1337643

ABSTRACT

Microbial translocation (MT) and intestinal damage (ID) are poorly explored in COVID-19. Aims were to assess whether alteration of gut permeability and cell integrity characterize COVID-19 patients, whether it is more pronounced in severe infections and whether it influences the development of subsequent bloodstream infection (BSI). Furthermore, we looked at the potential predictive role of TM and ID markers on Intensive Care Unit (ICU) admission and in-hospital mortality. Over March-July 2020, 45 COVID-19 patients were enrolled. Markers of MT [LPB (Lipopolysacharide Binding Protein) and EndoCab IgM] and ID [I-FABP (Intestinal Fatty Acid Binding Protein)] were evaluated at COVID-19 diagnosis and after 7 days. As a control group, age- and gender-matched healthy donors (HDs) enrolled during the same study period were included. Median age was 66 (56-71) years. Twenty-one (46.6%) were admitted to ICU and mortality was 22% (10/45). Compared to HD, a high degree of MT and ID was observed. ICU patients had higher levels of MT, but not of ID, than non-ICU ones. Likewise, patients with BSI had lower EndoCab IgM than non-BSI. Interestingly, patients with high degree of MT and low ID were likely to be admitted to ICU (AUC 0.822). Patients with COVID-19 exhibited high level of MT, especially subjects admitted to ICU. COVID-19 is associated with gut permeability.


Subject(s)
COVID-19/metabolism , Intestinal Mucosa/metabolism , SARS-CoV-2/physiology , Acute-Phase Proteins/metabolism , Aged , Biomarkers/metabolism , COVID-19/diagnosis , COVID-19/mortality , COVID-19/pathology , Carrier Proteins/metabolism , Disease Progression , Fatty Acid-Binding Proteins/metabolism , Female , Humans , Intensive Care Units , Intestinal Mucosa/pathology , Male , Membrane Glycoproteins/metabolism , Middle Aged , Predictive Value of Tests , Prognosis , Survival Analysis , Tight Junctions/metabolism
2.
Chemotherapy ; 66(1-2): 24-32, 2021.
Article in English | MEDLINE | ID: covidwho-1147336

ABSTRACT

Respiratory and gastrointestinal symptoms are the predominant clinical manifestations of the coronavirus disease 2019 (COVID-19). Infecting intestinal epithelial cells, the severe acute respiratory syndrome coronavirus-2 may impact on host's microbiota and gut inflammation. It is well established that an imbalanced intestinal microbiome can affect pulmonary function, modulating the host immune response ("gut-lung axis"). While effective vaccines and targeted drugs are being tested, alternative pathophysiology-based options to prevent and treat COVID-19 infection must be considered on top of the limited evidence-based therapy currently available. Addressing intestinal dysbiosis with a probiotic supplement may, therefore, be a sensible option to be evaluated, in addition to current best available medical treatments. Herein, we summed up pathophysiologic assumptions and current evidence regarding bacteriotherapy administration in preventing and treating COVID-19 pneumonia.


Subject(s)
COVID-19 , Dysbiosis , Gastrointestinal Microbiome/immunology , Probiotics/pharmacology , COVID-19/immunology , COVID-19/physiopathology , COVID-19/prevention & control , Dietary Supplements , Dysbiosis/therapy , Dysbiosis/virology , Humans , SARS-CoV-2
3.
Front Nutr ; 7: 613928, 2020.
Article in English | MEDLINE | ID: covidwho-1052491

ABSTRACT

Background: Mounting evidence suggests SARS-CoV-2 may impact on host microbiota and gut inflammation, infecting intestinal epithelial cells. This possible link and its implications can be investigated by observing the effects of modulation of the microbial flora in patients with COVID-19. The aim of this study was to compare the rate of mortality, the need of ICU hospitalization and the length of hospitalization in patients with severe COVID-19 pneumonia who received the best available therapy (BAT) vs. patients treated with BAT and supplemented with oral bacteriotherapy. Methods: This retrospective, observational cohort study included 200 adults with severe COVID-19 pneumonia. All patients received therapeutic regimens including low molecular weight heparin plus one or more between hydroxychloroquine, azithromycin, antivirals, and Tocilizumab. Oral bacteriotherapy was used as complementary treatment. Results: Out of the 200 patients, 112 received BAT without oral bacteriotherapy, and 88 BAT with oral bacteriotherapy. Crude mortality was 22%. Eleven percent died in the group of patients treated with BAT plus oral bacteriotherapy vs. 30% subjects in the group of patients managed only with BAT (p < 0.001). By multivariate analysis, the age >65 years, CRP >41.8 mg/L, Platelets <150.000 mmc, and cardiovascular events were associated with the increased risk of mortality. Oral bacteriotherapy was an independent variable associated with a reduced risk for death. Despite large prospective trials are needed, this study highlights a possible role for oral bacteriotherapy in the management of patients hospitalized for COVID-19 pneumonia.

4.
Medicine (Baltimore) ; 99(36): e21803, 2020 Sep 04.
Article in English | MEDLINE | ID: covidwho-982498

ABSTRACT

RATIONALE: Complex immune dysregulation in interferon (IFN) and T cell response has been observed in human immunodeficiency virus (HIV-1)-infected patients as well as in coronavirus disease-2019 (COVID-19) patients. However, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)/HIV-1 coinfection has been described in only few cases worldwide and no data are available on immunological outcomes in HIV-1-patients infected with SARS-CoV-2. Hence, this study aims to compare type I IFN response and T cell activation levels between a SARS-CoV-2/HIV-1-coinfected female patient and age-matched HIV-1-positive or uninfected women. PATIENT CONCERNS: A 52-year-old woman diagnosed with SARS-CoV-2/HIV-1 coinfection, ten HIV-1-positive women and five age-matched-healthy individuals were enrolled in this study. DIAGNOSES: SARS-CoV-2 infection caused severe pneumonia in the second week of illness in HIV-1-positive patient under protease inhibitors. Chest high-resolution computed tomography images of the SARS-CoV-2/HIV-1-coinfected patient showed bilateral ground-glass opacities. INTERVENTIONS: SARS-CoV-2/HIV-1-coinfected female patient under darunavir/cobicistat regimen received a 7-days hydroxychloroquine therapy. Analysis of IFNα/ß mRNA levels and CD4 and CD8 T cell (CD38, human leukocyte antigen-DR [HLA-DR], CD38 HLA-DR) frequencies were performed by RT/real-time PCR assays and flow cytometry, respectively. Median relative difference (MRD) was calculated for each immunological variable. For values greater than reference, MRD should be a positive number and for values that are smaller, MRD should be negative. OUTCOMES: The severe pneumonia observed in SARS-CoV-2/HIV-1-positive patient under protease inhibitors was reversed by a 7-days hydroxychloroquine therapy. At the end of treatment, on day 7, patient reported resolution of fever, normalization of respiratory rate (14 breaths/min), and improved oxygen arterial pressure with a FiO2 of 30%. MRD values for IFNα/ß and CD4 and CD8 T cells expressing CD38 and/or HLA-DR found in SARS-CoV-2-/HIV-1-coinfected woman were approximatively equal to 0 when refereed respectively to HIV-1-positive female patients [MRDs IFNα/ß: median -0.2545 (range: -0.5/0.1); T cells: median -0.11 (range: -0.8/1.3)] and ≥ 6 when referred to healthy individuals [MRDs IFNα/ß: median 28.45 (range: 15/41.9); T cells: median 10 (range 6/22)]. LESSONS: These results indicate that SARS-CoV-2 infection in HIV-1-positive female patient was associated with increased levels of IFNα/ß-mRNAs and T cell activation compared to healthy individuals.


Subject(s)
Coronavirus Infections/complications , HIV Infections/complications , Pneumonia, Viral/complications , Severe Acute Respiratory Syndrome/complications , Anti-Retroviral Agents/therapeutic use , Betacoronavirus , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/metabolism , COVID-19 , Case-Control Studies , Coronavirus Infections/drug therapy , Enzyme Inhibitors/therapeutic use , Female , HIV Infections/drug therapy , Humans , Hydroxychloroquine/therapeutic use , Interferons/blood , Lymphocyte Activation , Middle Aged , Pandemics , Pneumonia, Viral/drug therapy , RNA, Messenger , Real-Time Polymerase Chain Reaction , SARS-CoV-2 , Severe Acute Respiratory Syndrome/drug therapy , Severe Acute Respiratory Syndrome/virology
5.
J Med Virol ; 93(4): 2210-2220, 2021 04.
Article in English | MEDLINE | ID: covidwho-893240

ABSTRACT

The evaluation of new therapeutic resources against coronavirus disease 2019 (COVID-19) represents a priority in clinical research considering the minimal options currently available. To evaluate the adjuvant use of systemic oxygen-ozone administration in the early control of disease progression in patients with COVID-19 pneumonia. PROBIOZOVID is an ongoing, interventional, randomized, prospective, and double-arm trial enrolling patient with COVID-19 pneumonia. From a total of 85 patients screened, 28 were recruited. Patients were randomly divided into ozone-autohemotherapy group (14) and control group (14). The procedure consisted in a daily double-treatment with systemic Oxygen-ozone administration for 7 days. All patients were treated with ad interim best available therapy. The primary outcome was delta in the number of patients requiring orotracheal-intubation despite treatment. Secondary outcome was the difference of mortality between the two groups. Moreover, hematological parameters were compared before and after treatment. No differences in the characteristics between groups were observed at baseline. As a preliminary report we have observed that one patient for each group needed intubation and was transferred to ITU. No deaths were observed at 7-14 days of follow up. Thirty-day mortality was 8.3% for ozone group and 10% for controls. Ozone therapy did not significantly influence inflammation markers, hematology profile, and lymphocyte subpopulations of patients treated. Ozone therapy had an impact on the need for the ventilatory support, although did not reach statistical significance. Finally, no adverse events related to the use of ozone-autohemotherapy were reported. Preliminary results, although not showing statistically significant benefits of ozone on COVID-19, did not report any toxicity.


Subject(s)
COVID-19/drug therapy , Oxygen/administration & dosage , Ozone/administration & dosage , COVID-19/blood , COVID-19/virology , Female , Humans , Lymphocyte Subsets/drug effects , Male , Middle Aged , Oxygen/adverse effects , Ozone/adverse effects , Probiotics/administration & dosage , SARS-CoV-2/isolation & purification
7.
Front Med (Lausanne) ; 7: 389, 2020.
Article in English | MEDLINE | ID: covidwho-685804

ABSTRACT

Background: Gastrointestinal disorders are frequent in COVID-19 and SARS-CoV-2 has been hypothesized to impact on host microbial flora and gut inflammation, infecting intestinal epithelial cells. Since there are currently no coded therapies or guidelines for treatment of COVID-19, this study aimed to evaluate the possible role of a specific oral bacteriotherapy as complementary therapeutic strategy to avoid the progression of COVID-19. Methods: We provide a report of 70 patients positive for COVID-19, hospitalized between March 9th and April 4th, 2020. All the patients had fever, required non-invasive oxygen therapy and presented a CT lung involvement on imaging more than 50%. Forty-two patients received hydroxychloroquine, antibiotics, and tocilizumab, alone or in combination. A second group of 28 subjects received the same therapy added with oral bacteriotherapy, using a multistrain formulation. Results: The two cohorts of patients were comparable for age, sex, laboratory values, concomitant pathologies, and the modality of oxygen support. Within 72 h, nearly all patients treated with bacteriotherapy showed remission of diarrhea and other symptoms as compared to less than half of the not supplemented group. The estimated risk of developing respiratory failure was eight-fold lower in patients receiving oral bacteriotherapy. Both the prevalence of patients transferred to ICU and mortality were higher among the patients not treated with oral bacteriotherapy. Conclusions: A specific bacterial formulation showed a significant ameliorating impact on the clinical conditions of patients positive for SARS-CoV-2 infection. These results also stress the importance of the gut-lung axis in controlling the COVID-19 disease.

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