Targeting the Microbiome With KB109 in Outpatients with Mild to Moderate COVID-19 Reduced Medically Attended Acute Care Visits and Improved Symptom Duration in Patients With Comorbidities

  1. John P. Haran
  2. Yan Zheng
  3. Katharine Knobil
  4. Norma Alonzo Palma
  5. Jonathan F. Lawrence
  6. Mark A. Wingertzahn

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Abstract

Introduction

In 2020, the world experienced the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as the coronavirus disease 2019 (COVID-19) pandemic. Mounting evidence indicates that the gut microbiome plays a role in host immune response to infections and, in turn, may have an impact on the disease trajectory of SARS-CoV2 infection. However, it remains to be established whether modulation of the microbiome can impact COVID-19–related symptomatology and patient outcomes. Therefore, we conducted a study designed to modulate the microbiome evaluating the safety and physiologic effects of KB109 combined with self-supportive care (SSC) vs SSC alone in non-hospitalized patients with mild to moderate COVID-19. KB109 is a novel synthetic glycan developed to increase the production of gut microbial metabolites that support immune system homeostasis through gut microbiome modulation. Our goal was to gain a better understanding of the safety of KB109, the natural course of COVID-19 symptomatology, and the possible role of the gut microbiome in patients with mild to moderate COVID-19.

Methods

Adult patients who tested positive for COVID-19 were randomized 1:1 to receive KB109 combined with SSC or SSC alone for 14 days and were then followed for an additional 21 days (35 days in total). Patients self-assessed their COVID-19–related symptoms (8 cardinal symptoms plus 5 additional symptoms) and self-reported comorbidities. The primary and secondary objectives were to evaluate the safety of KB109 plus SSC compared with that of SSC alone and to evaluate selected measures of health, respectively.

Results

Between July 2, 2020 and December 23, 2020, 350 patients were randomized to receive KB109 and SSC (n=174) or SSC alone (n=176). Overall, the most common comorbidities reported were hypertension (18.0% [63/350 patients]) followed by chronic lung disease (8.6% 30/350 patients). KB109 was well tolerated with most treatment-emergent adverse events being mild to moderate in severity. The administration of KB109 plus SSC reduced medically-attended visits (ie, hospitalization, emergency room visits, or urgent care visits) by 50.0% in the overall population and by 61.7% in patients with ≥1 comorbidity; in patients aged ≥45 years or with ≥1 comorbidity, medically-attended visits were reduced by 52.8%, In the SSC group, patients reporting ≥1 comorbidity had a longer median time to resolution of symptoms than those who reported no comorbidities at baseline (13 overall symptoms: 30 vs 21 days, respectively; hazard ratio [HR]=1.163 [95% CI, 0.723-1.872]; 8 cardinal symptoms: 21 vs 15 days, respectively; HR=1.283 [95% CI, 0.809-2.035]). In patients reporting ≥1 comorbidity, median time to resolution of symptoms was shorter in the KB109 plus SSC group compared with the SSC alone group (13 overall symptoms: 30 vs 21 days, respectively; HR=1.422 [95% CI, 0.898-2.250]; 8 cardinal symptoms: 17 vs 21 days, respectively; HR=1.574 [95% CI, 0.997-2.485]). In the KB109 plus SSC group, patients aged ≥45 years or with ≥1 comorbidity had a shorter median time to resolution of symptoms compared with SSC alone (overall 13 symptoms: 21 vs 31 days; HR=1.597 [95% CI, 1.064-2.398]).

Conclusions

Results from our study show that KB109 is well tolerated among patients with mild to moderate COVID-19. Patients with ≥1 comorbidity had a longer duration of COVID-19 symptoms than those without comorbidities. Moreover, in patients reporting ≥1 comorbidity or aged ≥45 years (at-risk population), administration of KB109 plus SSC improved median time to resolution of COVID-19–related symptoms and reduced the rate of medically-attended visits compared with SSC alone.

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  1. ScreenIT

    SciScore for 10.1101/2021.03.26.21254422: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementConsent: Select exclusion criteria included patients likely to require hospitalization for COVID-19 or hospitalized for inpatient treatment or currently being evaluated for potential hospitalization at the time of informed consent for conditions other than COVID-19.
    IRB: Each study site obtained institutional review board approval before study initiation and each patient provided written consent for study participation.
    RandomizationStudy Design: KB109 was evaluated in a virtual, randomized, controlled, multi-site, open-label study (NCT04414124, ClinicalTrials.org).
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical Methods: Analyses were conducted using SAS Version 9.4 or later (SAS Institute, Inc, Cary, NC).
    SAS Institute
    suggested: (Statistical Analysis System, RRID:SCR_008567)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04414124Active, not recruitingA Clinical Study to Assess the Natural History of COVID-19 a…

    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.

    About SciScore

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  2. Version published to 10.1101/2021.03.26.21254422 on medRxiv