Gut and oral microbiota associations with viral mitigation behaviors during the COVID-19 pandemic.

Imposition of social and health behavior mitigations are important control measures in response to the coronavirus disease 2019 (COVID-19) pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Although postulated that these measures may impact the human microbiota including losses in diversity from heightened hygiene and social distancing measures, this hypothesis remains to be tested. Other impacts on the microbiota and host mental and physical health status associations from these measures are also not well-studied. Here we examine changes in stool and oral microbiota by analyzing 16S rRNA gene sequence taxonomic profiles from the same individuals during pre-pandemic (before March 2020) and early pandemic (May-November 2020) phases. During the early pandemic phase, individuals were also surveyed using questionnaires to report health histories, anxiety, depression, sleep and other lifestyle behaviors in a cohort of predominantly Caucasian adults (mean age = 61.5 years) with the majority reporting at least one underlying co-morbidity. We identified changes in microbiota (stool n = 288; oral n = 89) between pre-pandemic and early pandemic time points from the same subject and associated these differences with questionnaire responses using linear statistical models and hierarchical clustering of microbiota composition coupled to logistic regression. While a trend in loss of diversity was identified between pre-pandemic and early pandemic time points it was not statistically significant. Paired difference analyses between individuals identified fewer significant changes between pre-pandemic and early pandemic microbiota in those who reported fewer comorbidities. Cluster transition analyses of stool and saliva microbiota determined most individuals remained in the same cluster assignments from the pre-pandemic to early pandemic period. Individuals with microbiota that shifted in composition, causing them to depart a pre-pandemic cluster, reported more health issues and pandemic-associated worries. Collectively, our study identified that stool and saliva microbiota from the pre-pandemic to early pandemic periods largely exhibited ecological stability (especially stool microbiota) with most associations in loss of diversity or changes in composition related to more reported health issues and pandemic-associated worries. Longitudinal observational cohorts are necessary to monitor the microbiome in response to pandemics and changes in public health measures.

Plasma 1,3-ß-d-glucan levels predict adverse clinical outcomes in critical illness.

BACKGROUNDThe fungal cell wall constituent 1,3-ß-d-glucan (BDG) is a pathogen-associated molecular pattern that can stimulate innate immunity. We hypothesized that BDG from colonizing fungi in critically ill patients may translocate into the systemic circulation and be associated with host inflammation and outcomes.METHODSWe enrolled 453 mechanically ventilated patients with acute respiratory failure (ARF) without invasive fungal infection and measured BDG, innate immunity, and epithelial permeability biomarkers in serially collected plasma samples.RESULTSCompared with healthy controls, patients with ARF had significantly higher BDG levels (median [IQR], 26 pg/mL [15-49 pg/mL], P < 0.001), whereas patients with ARF with high BDG levels (≥40 pg/mL, 31%) had higher odds for assignment to the prognostically adverse hyperinflammatory subphenotype (OR [CI], 2.88 [1.83-4.54], P < 0.001). Baseline BDG levels were predictive of fewer ventilator-free days and worse 30-day survival (adjusted P < 0.05). Integrative analyses of fungal colonization and epithelial barrier disruption suggested that BDG may translocate from either the lung or gut compartment. We validated the associations between plasma BDG and host inflammatory responses in 97 hospitalized patients with COVID-19.CONCLUSIONBDG measurements offered prognostic information in critically ill patients without fungal infections. Further research in the mechanisms of translocation and innate immunity recognition and stimulation may offer new therapeutic opportunities in critical illness.FUNDINGUniversity of Pittsburgh Clinical and Translational Science Institute, COVID-19 Pilot Award and NIH grants (K23 HL139987, U01 HL098962, P01 HL114453, R01 HL097376, K24 HL123342, U01 HL137159, R01 LM012087, K08HK144820, F32 HL142172, K23 GM122069).