Prevalence and severity of diarrhea and clostridioides difficile infection in patients treated for covid-19 infection

Introduction: COVID-19, which is caused by infection with SARS-CoV-2 predominantly includes pulmonary symptoms;however, almost 10% of cases develop diarrhea. A US clinical surveillance study demonstrated high prevalence of Clostridioides difficile infection (CDI) in COVID-19 patients with the rate of 3.6/10,000 patient-days [1]. Antibiotics frequently used for COVID-19 infected patients (i.e. macrolides, cephalosporins and fluoroquinolones) are commonly associated to CDI. Aims & Methods: To evaluate the prevalence diarrhea and CDI in patients treated for COVID-19 infection. Overall 556 patients hospitalized to COVID hospital of Sechenov university were evaluated (mean age - 55.9, 20 to 96 years;m 46.8%, f 53.2%). CDI was diagnosed by enzyme immunoassay using monoclonal antibodies against Clostridioides difficile toxins A and B. Results: Overall (both during out- and in-hospital stage) 158 patients (28.4%) developed diarrhea 52 - before admission (9.4%), 107 - during hospitalization (19.2%). Overall 311 patients (55.9%) received antibiotics before admission to the hospital. 525 patients (94.3%) received antibiotics during hospital stay. During hospitalization macrolides were prescribed to 79,6% of patients, fluoroquinolones-36,3%, penicillins-15,8%, carbapenems-6,8%, 1st generation cephalosporins-0,4%, 3rd generation cephalosporins-61%, 4th generation cephalosporins-0,5%. No relation of out-patient antibiotic treatment to diarrhea developed during hospital stay was found. Following effects were found for in-hospital antibiotics: azithromycin demonstrated negative correlation to the risk of diarrhea development: OR=0.482 (95%CI=0.31-0.75, χ2=10,85, p=0.001). Other macrolides, but azithromycin: OR=0.340 (95%CI=0.12- 0.97, χ2=4,470, p=0.034. Penicillins: OR=0.921 (95%CI=0.51-1.66, χ2=0.07, p=NS). 3rd generation cephalosporins: OR=0.59 (95%CI=0.38-0.90, χ2=6.14, p=0.013). Fluoroquinolones: OR=1.23 (95%CI=0.80-1.89, χ2=0.85, p=NS). Carbapenems: OR=2.06 (95%CI=1.00-4.22, χ2=3.99, p=0.046). Of patients, who developed in-hospital diarrhea 61,3% were positive for CD toxin A, 54,8%-for toxin B, 45,2%-for both toxins A and B. No association of the in-hospital antibiotic group to the presence of CD toxins in patients with diarrhea was found. Conclusion: Research is needed to understand if, when, and how antibiotics should be used to treat COVID-19 patients while minimizing adverse effects such as CDI. CDI in COVID-19 patients should be investigated to identify risk factors such as use of specific antibiotics, previous CDI, and/or presentation of COVID-19 gastrointestinal symptoms. Pathogenesis of CD-associated colitis in COVID-19 patients may be related not only to the broad-spectrum antibiotic treatment, but to overall severity of the patient, length of hospital stay, presence of multi-organ failure and secondary vascular disorders.