Gastrointestinal involvement attenuates COVID-19 severity and mortality
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Abstract
Given that gastrointestinal (GI) symptoms are a prominent extrapulmonary manifestation of coronavirus disease 2019 (COVID-19), we investigated the impact of GI infection on disease pathogenesis in three large cohorts of patients in the United States and Europe. Unexpectedly, we observed that GI involvement was associated with a significant reduction in disease severity and mortality, with an accompanying reduction in key inflammatory proteins including IL-6, CXCL8, IL-17A and CCL28 in circulation. In a fourth cohort of COVID-19 patients in which GI biopsies were obtained, we identified severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) within small intestinal enterocytes for the first time in vivo but failed to obtain culturable virus. High dimensional analyses of GI tissues confirmed low levels of cellular inflammation in the GI lamina propria and an active downregulation of key inflammatory genes including IFNG, CXCL8, CXCL2 and IL1B among others. These data draw attention to organ-level heterogeneity in disease pathogenesis and highlight the role of the GI tract in attenuating SARS-CoV-2-associated inflammation with related mortality benefit.
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SciScore for 10.1101/2020.09.07.20187666: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Following homogenization and centrifugation (10,000 × g, 20 min, 4°C), the resulting supernatant tissue supernatant was inoculated onto Vero E6 monolayer maintained in optimal virus growth media for SARS-CoV-2 virus (DMEM w/ L-Glutamate Vero E6suggested: RRID:CVCL_XD71)Software and Algorithms Sentences Resources CyTOF Data analysis: De-barcoded files were uploaded to Cytobank for analyses. Cytobanksuggested: (Cytobank, RRID:SCR_014043)Res…
SciScore for 10.1101/2020.09.07.20187666: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Following homogenization and centrifugation (10,000 × g, 20 min, 4°C), the resulting supernatant tissue supernatant was inoculated onto Vero E6 monolayer maintained in optimal virus growth media for SARS-CoV-2 virus (DMEM w/ L-Glutamate Vero E6suggested: RRID:CVCL_XD71)Software and Algorithms Sentences Resources CyTOF Data analysis: De-barcoded files were uploaded to Cytobank for analyses. Cytobanksuggested: (Cytobank, RRID:SCR_014043)Results from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:While our data point to a novel aspect of COVID-19 pathogenesis, we would also like to mention a few limitations of our study. GI biopsies were not performed on a representative subset of the Discovery or Validation Cohorts, but rather from a distinct set of patients who were undergoing clinical indicated procedures. In addition, we recognize our analysis on intestinal mucosal samples were not performed during the most acute phase of the illness in some patients. A separate study by our group that analyzed stool samples from patients going through the acute phase of COVID-19, found little evidence of an active gut inflammatory response. In particular, such stool samples strikingly lacked any significant increase of IL-1β, IL-6, TNF-α and IL-10, despite the detection of viral genomes (MEDRXIV/2020/183947). Finally, in our clinical outcomes analysis we acknowledge that the reporting GI symptoms can be subject to individual variation and the clinical documentation might vary depending on providers and on the acuity of the patients’ presentation. While it is possible that GI symptoms might have been underreported in patients who were admitted directly to the ICU, our findings are in line with those observed in the External Validation Cohort where patients who died or were admitted to the ICU within 24 hours form initial presentation were excluded from the analysis. In summary, we have observed an unexpected but significant reduction in COVID-19 severity and mortality when patient...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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