Immunomodulatory Effects of Probiotics on COVID-19 Infection by Targeting the Gut-Lung Axis Microbial Cross-Talk.

The ecosystem of the human gastrointestinal tract, named gut microbiota, represents the most thoroughly mapped ecosystem. Perturbations on bacterial populations cause dysbiosis, a condition correlated to a wide range of autoimmune, neurological, metabolic, cardiovascular, and respiratory diseases. The lungs have their flora, which are directly related to the gut flora via bidirectional communication allowing the transport of microbial metabolites and toxins produced by intestinal bacteria through the circulation and lymphatic system. This mutual microbial cross-talk communication called the gut-lung axis modulates the immune and inflammatory response to infections. COVID-19 causes dysbiosis, altered intestinal permeability, and bacterial translocation. Dysbiosis, through the gut-lung axis, promotes hyper-inflammation, exacerbates lung damage, and worsens clinical outcomes. Preclinical and clinical studies have shown that probiotics can regulate cytokine secretion, thus affecting both nonspecific and specific immunity. Probiotics act by blocking the virus from invading and proliferating in host cells, by stimulating the immune response, and by suppressing the activation of NLRP3 inflammasome. Herein, we reviewed the evidence from preclinical and clinical studies evaluating the effect of probiotics administration on the immune response to COVID-19 infection by targeting the gut-lung axis microbial cross-talk.

Impact of COVID-19 pandemic on the healthcare and psychosocial well-being of patients with inflammatory bowel disease.

COVID-19 pandemic has resulted in unprecedented disruptions to several aspects of gastroenterology healthcare services worldwide. In particular, patients with inflammatory bowel disease (IBD) represent a sensitive population that must retain access to healthcare services to avoid potential disease exacerbation under the continuous threat of viral infection. Emerging evidence also highlights the severe impact on these patients' mental well-being, leading to a constant cycle of stress/depression and disease activity relapse. In an effort to circumvent these healthcare challenges in a newly-shaped environment, physicians implemented telemedicine consultative care programs as a novel alternative follow-up method highly favored by the patients. The situation is still far from perfect, since a large proportion of patients are lost to follow up and/or lose adherence to their medication, especially when the exact timeframe or optimal strategy for the post-COVID era remains to be defined. Cancelation of elective endoscopic procedures has led to a significant decline of new IBD diagnoses. This review summarizes the data on the global impact of COVID-19 on IBD patients' healthcare and their psychosocial status.

Management of Patients with Inflammatory Diseases during the COVID-19 Pandemic.

Patients with various inflammatory diseases of the gastrointestinal tract, skin, liver, kidneys, and musculoskeletal system-connective tissues, often undergo different anti-inflammatory therapies to maintain remission and avoid serious and/or life-threatening complications. Available data so far show an increased rate of hospitalization in such patients during the COVID19 pandemic. The key points of our position statement are summarized below: Patients with inflammatory diseases who receive moderate or high-risk anti-inflammatory therapies might be considered as an increased risk group for severe COVID-19 and appropriate measures should be taken in order to protect them. Initiation of immuno-suppressive/modulatory therapies should be done with caution, taking into account the severity of the underlying inflammatory disease, the type of anti-inflammatory treatment, and the risk of exposure to the SARS-CoV-2 virus. Discontinuation of anti-inflammatory therapies in patients who have not been exposed to or infected with the SARS-CoV-2 virus is not recommended. In patients who become infected with SARS-CoV-2, anti-inflammatory therapies should be discontinued, except in special cases. Specialty physicians should actively participate in the Interdisciplinary Teams caring for patients with inflammatory diseases during COVID19 infection.

Probiotics Regulating Inflammation via NLRP3 Inflammasome Modulation: A Potential Therapeutic Approach for COVID-19.

Inflammasomes are cytoplasmic multiprotein complexes formed by the host's immune system as a response to microbial infection and cellular damage. Many studies have revealed various regulators of NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation, while it has been recently shown that NLRP3 is implicated in COVID-19 pathogenesis. At the same time, probiotics counteract the inflammatory process and modulate cytokine release, thus influencing both innate and adaptive immune systems. Herein, we review the immunomodulatory potential of probiotics on the assembly of NLRP3 inflammasome, as well as the pathophysiological mechanisms supporting the use of probiotic bacteria for SARS-CoV-2 infection management, presenting evidence from preclinical studies of the last decade: in vivo, ex vivo, and mixed trials. Data show that probiotics intake is related to NLRP3 inflammasome attenuation and lower levels of inflammation markers, highlighting the beneficial effects of probiotics on inflammatory conditions. Currently, none of the ongoing clinical trials evaluating the effectiveness of probiotics intake in humans with COVID-19 has been completed. However, evidence from preclinical studies indicates that probiotics may block virus invasion and replication through their metabolites, bacteriocins, and their ability to block Angiotensin-Converting Enzyme 2 (ACE2), and by stimulating the immune response through NLRP3 inflammasome regulation. In this review, the beneficial effects of probiotics in the inflammatory process through NLRP3 inflammasome attenuation are presented. Furthermore, probiotics may target SARS-CoV-2 both by blocking virus invasion and replication and by stimulating the immune response through NLRP3 inflammasome regulation. Heterogeneity of the results-due to, among others, different bacterial strains and their metabolites, forms, dosage, and experimental designs-indicates the need for more extensive research.

COVID-19 in the endoscopy unit: How likely is transmission of infection? Results from an international, multicenter study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) significantly affected endoscopy practice, as gastrointestinal endoscopy is considered a risky procedure for transmission of infection to patients and personnel of endoscopy units (PEU). AIM: To assess the impact of COVID-19 on endoscopy during the first European lockdown (March-May 2020). METHODS: Patients undergoing endoscopy in nine endoscopy units across six European countries during the period of the first European lockdown for COVID-19 (March-May 2020) were included. Prior to the endoscopy procedure, participants were stratified as low- or high- risk for potential COVID-19 infection according to the European Society of Gastrointestinal Endoscopy (ESGE) and the European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA) joint statement, and contacted 7-14 d later to assess COVID-19 infection status. PEU were questioned regarding COVID-19 symptoms and/or infection via questionnaire, while information regarding hospitalizations, intensive care unit-admissions and COVID-19-related deaths were collected. The number of weekly endoscopies at each center during the lockdown period was also recorded. RESULTS: A total of 1267 endoscopies were performed in 1222 individuals across nine European endoscopy departments in six countries. Eighty-seven (7%) were excluded because of initial positive testing. Of the 1135 pre-endoscopy low risk or polymerase chain reaction negative for COVID-19, 254 (22.4%) were tested post endoscopy and 8 were eventually found positive, resulting in an infection rate of 0.7% [(95%CI: 0.2-0.12]. The majority (6 of the 8 patients, 75%) had undergone esophagogastroduodenoscopy. Of the 163 PEU, 5 [3%; (95%CI: 0.4-5.7)] tested positive during the study period. A decrease of 68.7% (95%CI: 64.8-72.7) in the number of weekly endoscopies was recorded in all centers after March 2020. All centers implemented appropriate personal protective measures (PPM) from the initial phases of the lockdown. CONCLUSION: COVID-19 transmission in endoscopy units is highly unlikely in a lockdown setting, provided endoscopies are restricted to emergency cases and PPM are implemented.

The natural history of COVID-19 in patients with inflammatory bowel disease: a nationwide study by the Hellenic Society for the study of IBD.

OBJECTIVES: COVID-19 has evolved into a global health crisis, variably affecting the management of patients with chronic illnesses. Patients with inflammatory bowel disease (IBD) may represent a vulnerable population due to frequent administration of immune-modifying treatments. We aimed to depict the natural history of COVID-19 infection in Greek patients with IBD at a nationwide level via unbiased reporting of all cases that were registered during the sequential waves of the pandemic. METHODS: Following a national call from the Hellenic Society for the study of IBD, we enrolled all IBD patients with established diagnoses of COVID-19. Clinical and epidemiological data, including COVID-19 modifying factors and IBD-associated therapies, were analyzed against adverse outcomes (hospitalization, ICU admission and death). RESULTS: We identified 154 IBD patients who were diagnosed with COVID-19 (men: 58.4%; mean age=41.7 years [SD = 14.9]; CD: 64.3%). Adverse outcomes were reported in 34 patients (22.1%), including 3 ICU admissions (1.9%) and two deaths (1.3%). Multivariate logistic regression analysis showed that age (OR = 1.04, 95% CI, 1-1.08) and dyspnea at presentation (OR = 7.36, 95% CI, 1.84-29.46) were associated with worse outcomes of COVID-19 infection. In contrast, treatment with biologics, in particular anti-TNF agents, exerted a protective effect against an unfavorable COVID-19 disease course (OR = 0.4, 95% CI, 0.16-0.99). Patients on subcutaneous biologics were more likely to halt treatment due to the infection as compared to those on intravenous biologics. CONCLUSIONS: IBD patients who developed COVID-19 had a benign course with adverse outcomes being infrequent. Treatment with anti-TNF biologics had a protective effect, thus, supporting continuation of therapy during the pandemic.

Differences between fellows and fellowship program directors in their perception of the impact of the COVID-19 pandemic on gastroenterology training: results from a nationwide survey in Greece.

BACKGROUND: Lockdown measures applied during the SARS-CoV-2 outbreak caused a significant disturbance to hospital routine. We assessed trainees' and fellowship directors' perceptions regarding the impact of the pandemic on gastroenterology fellowship training. METHODS: A web-based survey was anonymously disseminated to all Greek gastroenterology fellows and fellowship program directors. Participants completed electronically a questionnaire comprised of 5 domains that assessed participants' perception of: 1) overall impact on training; 2) impact on training in gastroenterology-specific fields (endoscopy, inflammatory bowel disease, hepatology); 3) impact on different aspects of endoscopy training; 4) impact on academic training; and 5) training perspectives for the post-pandemic era. RESULTS: A total of 77/128 fellows (60.1%) and 18/28 fellowship program directors (64.3%) responded. More fellows reported that the COVID-19 pandemic would have an adverse impact on fellowship training compared to their fellowship program directors (81.8% vs. 55.6%, P=0.038). This concern was mainly focused on endoscopy training (83.1% vs. 27.8%, P<0.001), with no difference regarding training in gastroenterology's other specific fields. The difference was consistent for technical skills (79.2% vs. 38.9%, P=0.001), and for the performance of basic diagnostic (70.1% vs. 22.2%, P<0.001) and emergency (48.1% vs. 11.1%, P=0.004) procedures. Fellows and fellowship program directors identified the unknown timeframe of measure implementation and the postponement of scheduled endoscopic procedures as the main factors that negatively affected training. Extension of the fellowship training program was deemed the optimal option by fellows for addressing the training decrement in the post-pandemic era, while fellowship program directors favored an increase in workload. CONCLUSION: Fellows and their fellowship program directors do not share the same concerns about the impact of COVID-19 pandemic on training programs and they propose different measures to remedy its effects.

"Missing" acute coronary syndrome hospitalizations during the COVID-19 era in Greece: Medical care avoidance combined with a true reduction in incidence?

BACKGROUND: Reports from countries severely hit by the COVID-19 pandemic suggest a decline in acute coronary syndrome (ACS)-related hospitalizations. The generalizability of this observation on ACS admissions and possible related causes in countries with low COVID-19 incidence are not known. HYPOTHESIS: ACS admissions were reduced in a country spared by COVID-19. METHODS: We conducted a nationwide study on the incidence rates of ACS-related admissions during a 6-week period of the COVID-19 outbreak and the corresponding control period in 2019 in Greece, a country with strict social measures, low COVID-19 incidence, and no excess in mortality. RESULTS: ACS admissions in the COVID-19 (n = 771) compared with the control (n = 1077) period were reduced overall (incidence rate ratio [IRR]: 0.72, P < .001) and for each ACS type (ST-segment elevation myocardial infarction [STEMI]: IRR: 0.76, P = .001; non-STEMI: IRR: 0.74, P < .001; and unstable angina [UA]: IRR: 0.63, P = .002). The decrease in STEMI admissions was stable throughout the COVID-19 period (temporal correlation; R2 = 0.11, P = .53), whereas there was a gradual decline in non-STEMI/UA admissions (R2 = 0.75, P = .026) following the progressively stricter social measures. During the COVID-19 period, patients admitted with ACS presented more frequently with left ventricular systolic impairment (22.2 vs 15.5% control period; P < .001). CONCLUSIONS: We observed a reduction in ACS hospitalizations during the COVID-19 outbreak in a country with strict social measures, low community transmission, and no excess in mortality. Medical care avoidance behavior is an important factor for these observations, while a true reduction of the ACS incidence due to self-isolation/quarantining may have also played a role.

ESGE and ESGENA Position Statement on gastrointestinal endoscopy and the COVID-19 pandemic.

We are currently living in the throes of the COVID-19 pandemic that imposes a significant stress on health care providers and facilities. Europe is severely affected with an exponential increase in incident infections and deaths. The clinical manifestations of COVID-19 can be subtle, encompassing a broad spectrum from asymptomatic mild disease to severe respiratory illness. Health care professionals in endoscopy units are at increased risk of infection from COVID-19. Infection prevention and control has been shown to be dramatically effective in assuring the safety of both health care professionals and patients. The European Society of Gastrointestinal Endoscopy (www.esge.com) and the European Society of Gastroenterology and Endoscopy Nurses and Associates (www.esgena.org) are joining forces to provide guidance during this pandemic to help assure the highest level of endoscopy care and protection against COVID-19 for both patients and endoscopy unit personnel. This guidance is based upon the best available evidence regarding assessment of risk during the current status of the pandemic and a consensus on which procedures to perform and the priorities on resumption. We appreciate the gaps in knowledge and evidence, especially on the proper strategy(ies) for the resumption of normal endoscopy practice during the upcoming phases and end of the pandemic and therefore a list of potential research questions is presented. New evidence may result in an updated statement.