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  1. Article ; Online: Intestinal Host Response to SARS-CoV-2 Infection and COVID-19 Outcomes in Patients With Gastrointestinal Symptoms.

    Livanos, Alexandra E / Jha, Divya / Cossarini, Francesca / Gonzalez-Reiche, Ana S / Tokuyama, Minami / Aydillo, Teresa / Parigi, Tommaso L / Ladinsky, Mark S / Ramos, Irene / Dunleavy, Katie / Lee, Brian / Dixon, Rebekah E / Chen, Steven T / Martinez-Delgado, Gustavo / Nagula, Satish / Bruce, Emily A / Ko, Huaibin M / Glicksberg, Benjamin S / Nadkarni, Girish /
    Pujadas, Elisabet / Reidy, Jason / Naymagon, Steven / Grinspan, Ari / Ahmad, Jawad / Tankelevich, Michael / Bram, Yaron / Gordon, Ronald / Sharma, Keshav / Houldsworth, Jane / Britton, Graham J / Chen-Liaw, Alice / Spindler, Matthew P / Plitt, Tamar / Wang, Pei / Cerutti, Andrea / Faith, Jeremiah J / Colombel, Jean-Frederic / Kenigsberg, Ephraim / Argmann, Carmen / Merad, Miriam / Gnjatic, Sacha / Harpaz, Noam / Danese, Silvio / Cordon-Cardo, Carlos / Rahman, Adeeb / Schwartz, Robert E / Kumta, Nikhil A / Aghemo, Alessio / Bjorkman, Pamela J / Petralia, Francesca / van Bakel, Harm / Garcia-Sastre, Adolfo / Mehandru, Saurabh

    Gastroenterology

    2021  Volume 160, Issue 7, Page(s) 2435–2450.e34

    Abstract: ... manifestation of COVID-19, we investigated intestinal infection with SARS-CoV-2, its effect on pathogenesis, and ... in patients with and without GI symptoms in 2 large, independent cohorts of hospitalized patients ... In parallel, reduced mortality in patients with COVID-19 presenting with GI symptoms was observed. A potential ...

    Abstract Background & aims: Given that gastrointestinal (GI) symptoms are a prominent extrapulmonary manifestation of COVID-19, we investigated intestinal infection with SARS-CoV-2, its effect on pathogenesis, and clinical significance.
    Methods: Human intestinal biopsy tissues were obtained from patients with COVID-19 (n = 19) and uninfected control individuals (n = 10) for microscopic examination, cytometry by time of flight analyses, and RNA sequencing. Additionally, disease severity and mortality were examined in patients with and without GI symptoms in 2 large, independent cohorts of hospitalized patients in the United States (N = 634) and Europe (N = 287) using multivariate logistic regressions.
    Results: COVID-19 case patients and control individuals in the biopsy cohort were comparable for age, sex, rates of hospitalization, and relevant comorbid conditions. SARS-CoV-2 was detected in small intestinal epithelial cells by immunofluorescence staining or electron microscopy in 15 of 17 patients studied. High-dimensional analyses of GI tissues showed low levels of inflammation, including down-regulation of key inflammatory genes including IFNG, CXCL8, CXCL2, and IL1B and reduced frequencies of proinflammatory dendritic cells compared with control individuals. Consistent with these findings, we found a significant reduction in disease severity and mortality in patients presenting with GI symptoms that was independent of sex, age, and comorbid illnesses and despite similar nasopharyngeal SARS-CoV-2 viral loads. Furthermore, there was reduced levels of key inflammatory proteins in circulation in patients with GI symptoms.
    Conclusions: These data highlight the absence of a proinflammatory response in the GI tract despite detection of SARS-CoV-2. In parallel, reduced mortality in patients with COVID-19 presenting with GI symptoms was observed. A potential role of the GI tract in attenuating SARS-CoV-2-associated inflammation needs to be further examined.
    MeSH term(s) Aged ; Aged, 80 and over ; COVID-19/diagnosis ; COVID-19/immunology ; COVID-19/mortality ; COVID-19/virology ; Case-Control Studies ; Cells, Cultured ; Cytokines/blood ; Female ; Gastrointestinal Diseases/diagnosis ; Gastrointestinal Diseases/immunology ; Gastrointestinal Diseases/mortality ; Gastrointestinal Diseases/virology ; Host-Pathogen Interactions ; Humans ; Immunity, Mucosal ; Inflammation Mediators/blood ; Intestinal Mucosa/immunology ; Intestinal Mucosa/virology ; Italy ; Male ; Middle Aged ; New York City ; Prognosis ; Risk Assessment ; Risk Factors ; SARS-CoV-2/immunology ; SARS-CoV-2/pathogenicity ; Viral Load
    Chemical Substances Cytokines ; Inflammation Mediators
    Language English
    Publishing date 2021-03-04
    Publishing country United States
    Document type Journal Article ; Multicenter Study ; Research Support, N.I.H., Extramural
    ZDB-ID 80112-4
    ISSN 1528-0012 ; 0016-5085
    ISSN (online) 1528-0012
    ISSN 0016-5085
    DOI 10.1053/j.gastro.2021.02.056
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Gastrointestinal symptoms and digestive comorbidities in an Italian cohort of patients with COVID-19.

    Papa, A / Covino, M / Pizzolante, F / Miele, L / Lopetuso, L R / Bove, V / Iorio, R / Simeoni, B / Vetrone, L M / Tricoli, L / Mignini, I / Schepis, T / D'Alessandro, A / Coppola, G / Nicoletti, T / Visconti, E / Rapaccini, G

    European review for medical and pharmacological sciences

    2020  Volume 24, Issue 13, Page(s) 7506–7511

    Abstract: ... SARS-COV-2, and the occurrence of GI symptoms might be linked to a faster reduction of the viral load ... the association of GI-symptoms and digestive comorbidities with clinical outcomes.: Patients and methods ... the prevalence of GI symptoms among COVID-19 patients was 8.8%. During hospitalization, the frequency of GI ...

    Abstract Objective: The Coronavirus Disease 2019 (COVID-19) pandemic mainly involves respiratory symptoms, though gastrointestinal (GI) symptoms are increasingly being recognized. In this context, the presence of comorbidities appears to be associated with adverse outcomes. However, the role of digestive manifestations is not yet well defined. The primary aim of this study was to assess the prevalence of GI symptoms and digestive comorbidities in a cohort of patients with COVID-19 compared to controls. The secondary aim was to determine the association of GI-symptoms and digestive comorbidities with clinical outcomes.
    Patients and methods: Inpatients with COVID-19 and controls with similar symptoms and/or radiological findings were enrolled. Symptoms at admission and throughout hospitalization were collected as they were comorbidities. The measured clinical outcomes were mortality, intensive care unit admission and cumulative endpoint.
    Results: A total of 105 patients were included: 34 with COVID-19 and 71 controls. At admission, the prevalence of GI symptoms among COVID-19 patients was 8.8%. During hospitalization, the frequency of GI symptoms was higher in patients with COVID-19 than in controls (p=0.004). Among patients with COVID-19, the mortality and a cumulative endpoint rates of those with GI symptoms were both lower than for those without GI symptoms (p=0.016 and p=0.000, respectively). Finally, we found digestive comorbidities to be associated with a milder course of COVID-19 (p=0.039 for cumulative endpoint).
    Conclusions: Our results highlighted the non-negligible frequency of GI symptoms in patients with COVID-19, partly attributable to the therapies implemented. In addition, the presence of GI symptoms and digestive comorbidities is associated with better outcomes. Most likely, digestive comorbidities do not hinder the host's immune response against SARS-COV-2, and the occurrence of GI symptoms might be linked to a faster reduction of the viral load via the faecal route.
    MeSH term(s) Aged ; Aged, 80 and over ; Antiviral Agents/pharmacology ; Betacoronavirus/drug effects ; COVID-19 ; Case-Control Studies ; Cohort Studies ; Comorbidity ; Coronavirus Infections/diagnosis ; Coronavirus Infections/drug therapy ; Coronavirus Infections/epidemiology ; Female ; Gastrointestinal Diseases/diagnosis ; Gastrointestinal Diseases/drug therapy ; Gastrointestinal Diseases/epidemiology ; Humans ; Italy ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Pandemics ; Pneumonia, Viral/diagnosis ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/epidemiology ; Prospective Studies ; SARS-CoV-2
    Chemical Substances Antiviral Agents
    Keywords covid19
    Language English
    Publishing date 2020-07-15
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 605550-3
    ISSN 2284-0729 ; 1128-3602 ; 0392-291X
    ISSN (online) 2284-0729
    ISSN 1128-3602 ; 0392-291X
    DOI 10.26355/eurrev_202007_21923
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Host Response to SARS-CoV2 and Emerging Variants in Pre-Existing Liver and Gastrointestinal Diseases.

    Nayak, Baibaswata / Lal, Geetanjali / Kumar, Sonu / Das, Chandan J / Saraya, Anoop / Shalimar

    Frontiers in cellular and infection microbiology

    2021  Volume 11, Page(s) 753249

    Abstract: ... We aim to review the emerging variants of SARS-CoV2 and host response in patients with pre-existing liver ... predominant in the population, which can alter COVID-19 outcome due to altered immune status and host response ... features of new SARS-CoV2 variants, mechanisms of infection and host immune response, GI and hepatic ...

    Abstract Background: Novel coronavirus SARS-CoV2 is evolving continuously with emergence of several variants of increasing transmission capabilities and pandemic potential. Generation of variants occurs through accumulation of mutations due to the RNA nature of viral genome, which is further enhanced by variable selection pressures of this ongoing pandemic. COVID-19 presentations of SARS-CoV2 are mainly pulmonary manifestations with or without mild gastrointestinal (GI) and hepatic symptoms. However, the virus has evolved beyond pulmonary manifestations to multisystem disorder due to systemic inflammation and cytokine storm. Definitive cause of acute or late onset of inflammation, infection in various organs, and host response to emerging variants lacks clarity and needs elucidation. Several studies have reported underlying diseases including diabetes, hypertension, obesity, cardio- and cerebrovascular disorders, and immunocompromised conditions as significant risk factors for severe form of COVID-19. Pre-existing liver and GI diseases are also highly predominant in the population, which can alter COVID-19 outcome due to altered immune status and host response. We aim to review the emerging variants of SARS-CoV2 and host response in patients with pre-existing liver and GI diseases.
    Methods: In this review, we have elucidated the emergence and characteristic features of new SARS-CoV2 variants, mechanisms of infection and host immune response, GI and hepatic manifestation with radiologic features of COVID-19, and outcomes in pre-existing liver and GI diseases.
    Key findings: Emerging variants of concern (VOC) have shown increased transmissibility and virulence with severe COVID-19 presentation and mortality. There is a drastic swift of variants from the first wave to the next wave of infections with predominated major VOC including alpha (B.1.1.7, UK), beta (B.1.351, South Africa), gamma (B.1.1.28.1, Brazil), and delta (B1.1.617, India) variants. The mutations in the spike protein of VOC are implicated for increased receptor binding (N501Y, P681R) and immune escape (L452R, E484K/Q, T478K/R) to host response. Pre-existing liver and GI diseases not only have altered tissue expression and distribution of viral entry ACE2 receptor but also host protease TMPRSS2, which is required for both spike protein binding and cleavage to initiate infection. Altered immune status due to pre-existing conditions results in delayed virus clearance or prolonged viremia. Even though GI and hepatic manifestations of SARS-CoV2 are less severe, the detection of virus in patient's stool indicates GI tropism, replication, and shedding from the GI tract. COVID-19-induced liver injury, acute hepatic decompensation, and incidences of acute-on-chronic liver failure may change the disease outcomes.
    Conclusions: The changes in the spike protein of emerging variants, immunomodulation by viral proteins, and altered expression of host viral entry receptor in pre-existing diseases are the key determinants of host response to SARS-CoV2 and its disease outcome.
    MeSH term(s) COVID-19 ; Gastrointestinal Diseases ; Humans ; Immunity ; Liver ; RNA, Viral ; SARS-CoV-2
    Chemical Substances RNA, Viral
    Language English
    Publishing date 2021-10-25
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2619676-1
    ISSN 2235-2988 ; 2235-2988
    ISSN (online) 2235-2988
    ISSN 2235-2988
    DOI 10.3389/fcimb.2021.753249
    Database MEDical Literature Analysis and Retrieval System OnLINE

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