ABSTRACT
Introduction: Intestinal Microbiota Influences Both Susceptibility And Severity Of Bacterial And Viral-Induced Pathogenicity, Including Respiratory Diseases. In This Study, We Investigated The Relationship Between Intestinal Microbiota And Sars-Cov-2-Mediated Pathogenicity In The United States, Majority African American Cohort. Hypothesis: Intestinal Microbiota Is Modulated By Sars-Cov-2 Infection And Is Related To Symptom Severity And Recovery From The Disease. Methods: We Conducted A Single-Institution Study, Prospectively Collecting Fecal Samples From 50 Sars-Cov-2 Infected Patients Within 3 Days Of Icu Admission And 9 Sars-Cov-2 Recovered Patients Upon Testing Negative For The Virus. Feces Of 34 Uninfected Subjects At The Hospital With Unrelated Respiratory Medical Conditions Were Used As Controls. Total Fecal Rna/Dna Was Extracted And Microbiota Composition Was Determined Using 16s Rrna Gene Sequencing Of The V1-V3 Region. The 16s Rdna Sequencing Reads Were Processed Using Dada2 To Generate Amplicon Sequence Variants (Asv). Rt-Pcr On Fecal Rna Using Two Sets Of Validated Primer/Probes Was Performed To Establish The Presence Or Absence Of Sars-Cov-2 Viral Rna. Results: The Fecal Microbial Composition Was Found To Be Significantly Different Between Sars-Cov-2 Patients And Controls (Permanova Fdr-P=0.004), Independent Of Treatments Such As Antibiotic Exposure. Peptoniphilus, Corynebacterium And Campylobacter Were Identified As The Three Most Significantly Enriched Genera In Covid Patients Compared To Controls. Actively Infected Patients Were Also Found To Have A Different Gut Microbiota Than Recovered Patients (Permanova Fdr-P=0.003), And The Most Enriched Genera In The Covid-19 Patients Was Campylobacter, With Agathobacter Being Enriched In The Recovered Patients. No Difference In Microbial Community Structure Between Recovered Patients And Uninfected Controls Was Observed (Permanova Fdr-P=0.93), With Phocea Being The Top Genus Associated With Patients Who Recovered From Covid-19. Furthermore, No Difference In Alpha Diversity Between The Three Groups Was Noticed. More Importantly, 24 Of The 50 Covid-19 Patients (48%) Tested Positive Via Rt-Qpcr For Fecal Sars-Cov-2 Rna. A Significant Difference In Gut Microbial Composition Between Sars-Cov-2 Positive And Negative Samples Was Observed, With Klebsiella And Agathobacter Being Enriched In The Positive Cohort And Phocea In The Negative Cohort. No Significant Associations Between Microbiome Composition And Disease Severity Or Proton Pump Inhibitor Treatment Were Found. Conclusion: The Intestinal Microbiota Is Sensitive To The Presence Of Sars-Cov-2, With Increased Relative Abundance Of Genera (Campylobacter, Klebsiella) Associated With Gi Disease. Further Studies Are Needed To Investigate The Functional Impact Of Deleterious Bacterial Genera In Sars-Cov-2 On Gi Health.
ABSTRACT
Rationale: Statins, anti-hypertensives, Proton pump inhibitors (PPIs) and H2 receptor antagonist (H2RAs) are amongst the most commonly prescribed medications for adults over the age of 50 (Kantor et al, 2015). PPI use was recently reported to have worse clinical outcomes during the COVID-19 pandemic (Lee et al, 2020). Before COVID-19, PPI use was associated with an increased risk of community acquired pneumonia (CAP) (Hertzig et al, 2009;Othman et al, 2016;Zirk-Sadowski et al, 2018). In this study, we examined the mortality risk associated with these four medications in hospitalized CAP patients not due to novel SARS-CoV-2 infection. Methods: We analyzed de-identified patient data from a research database of 6 hospitals in an integrated tertiary university healthcare system from January 1 to December 31, 2019. ICD-10 codes for CAP at the time of hospital admission were used to identify patients. A list of 17 variables relevant to outcome of CAP including demographic, comorbid conditions and medications of interests were extracted. Statistical analysis included Wilcoxon rank-sum tests, chi-squared tests, and multivariable logistic regression models were used to assess the mortality risk of all the factors. Results: Of 1223 patients admitted with CAP, the overall mortality rate was 19.9% (243/1223), baseline characteristics are shown in Table 1. There were 613 (50%) patients on PPIs, 551 (45%) on anti-hypertensives, 276 (23%) on H2RAs, and 271 (22%) on statins. PPI users had a mortality rate of 26.3% (161/613) vs 13.4% (82/610) in non-PPI users (p < 0.001). In multivariate analysis, PPI use without statins was not associated with increased mortality OR = 1.10 (0.76 to 1.60), while statin use without PPI was associated significant lower mortality: OR = 0.28 (0.13 to 0.59). This benefit was eliminated when statins and PPI were used together (OR = 0.86;95% CI of 0.53 to 1.39). Variables associated with increased mortality risk in the logistic regression model are: each decade of age (OR = 1.16;95% CI of 1.08 to 1.25), congestive heart failure OR = 2.09 (1.48 to 2.95), cancer (OR = 1.69;95% CI of 1.23 to 2.34), cardiovascular disease (OR = 2.18;95% CI of 1.27 to 3.75), and stroke (OR = 1.48;95% CI of 1.01 to 2.16). Conclusions: Statin use was associated with reduced mortality in patients with CAP, but the benefit was no longer present when combined with PPIs. The etiology for the increased mortality warrants further investigation.
ABSTRACT
Rationale Coronavirus disease 2019 (COVID-19) has disproportionally affected African Americans (AA), with underlying medical conditions and socioeconomic determinants of health believed to be major contributors (Price-Haywood et al, 2020). The use of proton pump inhibitors (PPIs) was recently found to be associated with increased risk and worse outcomes of SARS-CoV-2 infection (Almario et al, 2020;Luxenberger et al, 2020;Lee et al, 2020). Methods We performed a retrospective cohort analysis of patients hospitalized for SARS-CoV-2 in an integrated health system of six hospitals between March 15 and August 15, 2020. To determine predictive factors of mortality, a set of 17 covariates were selected on the basis of clinical relevance to COVID-19 outcomes. The indications for medication use were evaluated in a subset of research patients. Results In 694 hospitalized COVID-19 patients (median age = 58 yr, 46% men, 65% AA), an overall mortality rate was 17.4% (121/694). Logistic regression analysis identified age (aOR=1.66 per decade, p<0.001), race other than AA or white (aOR=3.03, p=0.002), cancer (aOR=2.22, p=0.008), diabetes (aOR=1.95, p=0.003), anti-HTN (aOR=0.46, p=0.001) and PPI use (aOR=2.72, p<0.001) as predictors of mortality. There was no significant mortality difference observed with the use of H2 receptor antagonists. Moreover, PPI use was associated with higher mortality risk in AA (aOR=4.16, 95% CI = 2.28 to 7.59) than in non-AA patients (aOR=1.62, 95% CI = 0.82, 3.19, p=0.04 for interaction) (see Figure 1). The prevalence of PPI use in African Americans (32.6%147/451) and non-AA patients (32.9%, 80/243) were comparable. No other associations were found to differ between the two groups. Indications for PPI use in 31 of 87 research participants were: erosive esophagitis / recent hemorrhage (13%), non-erosive GERD symptoms (45%) and NSAID prophylaxis (42%). Conclusion PPIs are frequently used medications with a growing list of complications. Their use is associated with significant mortality risk in AA COVID-19 patients, and should be reassessed during the pandemic. This risk was not seen in patients who received H2 receptor antagonists. The gastrointestinal tract is a potential site of SARSCoV- 2 entry and replication and this association warrants further study.