ABSTRACT
Background: SARS-COV-2 shedding in the stool long after clearance from the respiratory tract has been reported in several studies during the COVID-19 pandemic. This suggests a long tail of viral persistence in the GI tract even after a patient has tested negative via oronasal swabs. Most patients admitted to the ICU or wards for COVID-19 at Cedars-Sinai are placed on between 2-13 antimicrobials at admission in order to prevent secondary respiratory infections, leading us to question whether the effect of reducing or eliminating the gut microbiome during SARS-COV-2 infection may result in prolonged GI infection and longterm GI side-effects. Antibiotic pre-treatment in rodent studies has shown that flaviviruses persist longer in the GI tract in the absence of gut microbiota. Studies have also demonstrated that antibiotic pre-treatment attenuates the antibody responses to the flu vaccine in mice and humans. Collectively, this suggests a reduction or elimination of the gut the microbiota by antibiotics before or during viral infection can drive viral persistence in the GI tract. Methods: Longitudinal stool samples were collected from 29 COVID-19 in-patients (wards, n=12;ICU, n=17, n=79 stool samples total) and 9 non-COVID-19 in-patients admitted for other respiratory infections. Ten of 29 COVID-19 in-patients were antibiotic naive. Stool metagenomics, metabolomics, and SARS-COV-2 viral quantification by qPCR, and fecal calprotectin were measured and aligned with antibiotic exposure of each patient. Results: Our findings show that 72% of stool samples from COVID-19 patients that tested negative for SARS-COV-2 in the stool were never exposed to in-patient antibiotics. Fecal calprotectin was significantly higher in ICU-admitted COVID-19 patients compared to those in the wards and non-COVID-19 controls. The highest fecal calprotectin levels corresponded to nine samples from three ICU patients, all of whom were on the heaviest regimen of antibiotics and were positive for SARS-COV-2 in the stool. Expectedly, gut microbiota variance was explained largely by antibiotic status, but also independently by stool SARS-COV-2 status. We recruited an additional 34 patients during the delta variant surge, and these samples are currently being analyzed along with fecal metabolomics. Conclusion: The heavy-dose antibiotic regimen administered to COVID-19 in-patients is associated with viral persistence of SARS-COV-2 in the GI tract, suggesting an important role of the gut microbiome in excluding SARS-COV-2 from the GI tract, perhaps by competitive exclusion or promoting interferon responses. Intestinal inflammation was significantly greater in COVID-19 ICU patients, with the highest levels of fecal calprotectin correlating to the heaviest dose of antibiotics and presence of SARS-COV-2 in the stool.
ABSTRACT
Background: Severe obesity (Body Mass Index (BMI) ≥40 kg/m2) is associated with a higher risk of developing severe symptoms and complications of coronavirus disease 19 (COVID-19), independent of other illnesses. Despite this, patients with severe obesity are less likely to receive Veno-Venous Extra Corporeal Membrane Oxygenation (VV-ECMO) support for severe Acute Respiratory Distress Syndrome (ARDS). Given this paradox, we examined the impact of severe obesity on outcomes of adult patients who underwent VV-ECMO implantation for ARDS at our center. Methods: We reviewed our ECMO database from May 2013 through May 2020. Adults, who had received VV-ECMO, either in-house or through our mobile ECMO program, were included. We grouped patients into those with BMI ≥40 kg/m2 or not and compared survival at 48 hours, survival to hospital discharge, and hospital length of stay. We conducted multiple logistic and linear regression analyses to analyze the association with categorical and continuous variables, respectively, controlling for patient age, gender, and use of mobile ECMO. Results: We identified 112 consecutive adult VV-ECMO patients;median age was 48 (34, 59) years, 61 (54.5%) were male, 56 (50%) were started on ECMO in-house, the median BMI was 31.7 (27.6, 38.8) Kg/ m2;and 23 (20.5%) had a BMI ≥40 kg/m2. Survival at 48 hours and hospital discharge were 69.6% and 61.6%, respectively;and, median hospital length of stay was 20 (9, 33) days. Logistic regression showed no evidence of an association between severe obesity and either 48-hour (OR 1.04, 95% CI 0.37-2.96) or hospital discharge survival (OR 1.06, 95% CI 0.38-2.93). There was, however, a significant correlation between increasing BMI and longer total hospital length of stay (R2 = 0.34;p = 0.0002) which remained significant in linear regression (p = 0.0002) (Figure). Conclusions: We found no association between severe obesity and survival at 48-hour and hospital discharge in patients supported on VV-ECMO. Severe obesity was associated with a longer hospital stay, however. Our experience suggests that severe obesity alone should not exclude candidacy for VV-ECMO support.