TY - JOUR
T1 - Intestinal Host Response to SARS-CoV-2 Infection and COVID-19 Outcomes in Patients With Gastrointestinal Symptoms
AU - Livanos, Alexandra E.
AU - Jha, Divya
AU - Cossarini, Francesca
AU - Gonzalez-Reiche, Ana S.
AU - Tokuyama, Minami
AU - Aydillo, Teresa
AU - Parigi, Tommaso L.
AU - Ladinsky, Mark S.
AU - Ramos, Irene
AU - Dunleavy, Katie
AU - Lee, Brian
AU - Dixon, Rebekah E.
AU - Chen, Steven T.
AU - Martinez-Delgado, Gustavo
AU - Nagula, Satish
AU - Bruce, Emily A.
AU - Ko, Huaibin M.
AU - Glicksberg, Benjamin S.
AU - Nadkarni, Girish
AU - Pujadas, Elisabet
AU - Reidy, Jason
AU - Naymagon, Steven
AU - Grinspan, Ari
AU - Ahmad, Jawad
AU - Tankelevich, Michael
AU - Bram, Yaron
AU - Gordon, Ronald
AU - Sharma, Keshav
AU - Houldsworth, Jane
AU - Britton, Graham J.
AU - Chen-Liaw, Alice
AU - Spindler, Matthew P.
AU - Plitt, Tamar
AU - Wang, Pei
AU - Cerutti, Andrea
AU - Faith, Jeremiah J.
AU - Colombel, Jean Frederic
AU - Kenigsberg, Ephraim
AU - Argmann, Carmen
AU - Merad, Miriam
AU - Gnjatic, Sacha
AU - Harpaz, Noam
AU - Danese, Silvio
AU - Cordon-Cardo, Carlos
AU - Rahman, Adeeb
AU - Schwartz, Robert E.
AU - Kumta, Nikhil A.
AU - Aghemo, Alessio
AU - Bjorkman, Pamela J.
AU - Petralia, Francesca
AU - van Bakel, Harm
AU - Garcia-Sastre, Adolfo
AU - Mehandru, Saurabh
N1 - Publisher Copyright:
© 2021 AGA Institute
PY - 2021/6
Y1 - 2021/6
N2 - 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.
AB - 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.
KW - COVID-19
KW - GI infection
KW - GI symptoms
KW - SARS-CoV-2
KW - host immune response
KW - outcomes
UR - http://www.scopus.com/inward/record.url?scp=85104884557&partnerID=8YFLogxK
U2 - 10.1053/j.gastro.2021.02.056
DO - 10.1053/j.gastro.2021.02.056
M3 - Article
C2 - 33676971
AN - SCOPUS:85104884557
SN - 0016-5085
VL - 160
SP - 2435-2450.e34
JO - Gastroenterology
JF - Gastroenterology
IS - 7
ER -