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

{ 'institution': [{'name': 'medRxiv'}], 'indexed': { 'date-parts': [[2021, 12, 22]], 'date-time': '2021-12-22T10:56:19Z', 'timestamp': 1640170579934}, 'posted': {'date-parts': [[2021, 3, 29]]}, 'group-title': 'Infectious Diseases (except HIV/AIDS)', 'reference-count': 31, 'publisher': 'Cold Spring Harbor Laboratory', 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'short-container-title': [], 'accepted': {'date-parts': [[2021, 3, 29]]}, 'abstract': '<jats:title>Abstract</jats:title><jats:sec><jats:title>Introduction</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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]).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>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.</jats:p></jats:sec>', 'DOI': '10.1101/2021.03.26.21254422', 'type': 'posted-content', 'created': {'date-parts': [[2021, 3, 29]], 'date-time': '2021-03-29T13:25:19Z', 'timestamp': 1617024319000}, 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': [ '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'], 'prefix': '10.1101', 'author': [ { 'ORCID': 'http://orcid.org/0000-0001-7311-1121', 'authenticated-orcid': False, 'given': 'John P.', 'family': 'Haran', 'sequence': 'first', 'affiliation': []}, {'given': 'Yan', 'family': 'Zheng', 'sequence': 'additional', 'affiliation': []}, {'given': 'Katharine', 'family': 'Knobil', 'sequence': 'additional', 'affiliation': []}, {'given': 'Norma Alonzo', 'family': 'Palma', 'sequence': 'additional', 'affiliation': []}, {'given': 'Jonathan F.', 'family': 'Lawrence', 'sequence': 'additional', 'affiliation': []}, {'given': 'Mark A.', 'family': 'Wingertzahn', 'sequence': 'additional', 'affiliation': []}], 'member': '246', 'reference': [ { 'key': '2021033102150738000_2021.03.26.21254422v1.1', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/s11481-020-09944-5'}, { 'key': '2021033102150738000_2021.03.26.21254422v1.2', 'unstructured': 'Johns Hopkins. 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