Intestinal Damage, Inflammation and Microbiota Alteration during COVID-19 Infection.

BACKGROUND: The virus SARS-CoV-2 is responsible for respiratory disorders due to the fact that it mainly infects the respiratory tract using the Angiotensin-converting enzyme 2 (ACE2) receptors. ACE2 receptors are also highly expressed on intestinal cells, representing an important site of entry for the virus in the gut. Literature studies underlined that the virus infects and replicates in the gut epithelial cells, causing gastrointestinal symptoms such as diarrhea, abdominal pain, nausea/vomiting and anorexia. Moreover, the SARS-CoV-2 virus settles into the bloodstream, hyperactivating the platelets and cytokine storms and causing gut-blood barrier damage with an alteration of the gut microbiota, intestinal cell injury, intestinal vessel thrombosis leading to malabsorption, malnutrition, an increasing disease severity and mortality with short and long-period sequelae. CONCLUSION: This review summarizes the data on how SARS-CoV-2 effects on the gastrointestinal systems, including the mechanisms of inflammation, relationship with the gut microbiota, endoscopic patterns, and the role of fecal calprotectin, confirming the importance of the digestive system in clinical practice for the diagnosis and follow-up of SARS-CoV-2 infection.

Is BMI Associated with COVID-19 Severity? A Retrospective Observational Study.

BACKGROUND: Coronavirus-19 disease (COVID-19) is an infection with high morbidity and mortality. Obesity and low body mass index (BMI) have both been linked to severe COVID-19, but recent studies have failed to confirm these associations. OBJECTIVES: The aim of this study was to examine the relationship between BMI and disease progression in hospitalised patients with COVID-19. METHODS: We performed a monocentric, retrospective observational study at the Fondazione Policlinico Gemelli in Rome. We enrolled 1544 (977 men) patients who presented to the emergency department with a positive COVID-19 test between January and December 2021. We divided patients into five classes based on BMI. Demographic, clinical, laboratory, and radiological data were collected for all patients. RESULTS: Of the 1544 patients, 1297 recovered after hospitalization, whereas 247 (16%) died. Of those who died, 16/247 (6.5%) had a BMI below18.5 kg/m2, 72/247 (29%) had a BMI between 18.5 and 24.99 kg/m2, 103/247 (42%) had a BMI between 25 and 29.99 kg/m2, 36/247 (15%) had a BMI between 30 and 35 kg/m2, and 20/247 (8%) had a BMI above 35 kg/m2. After adjusting the results for age, sex, and concomitant diseases using multivariate logistic regression, we found a significantly increased risk of intensive care unit (ICU) admission in severely obese patients (BMI > 35) compared to normal weight patients (BMI: 18.5-24.99) (p > 0.001). Mortality was not associated with BMI. CONCLUSION: We confirm that severe obesity is a risk factor for ICU admission in patients with COVID-19. No association was found between BMI and mortality.

Prevalence and Outcome of Asthma in Adult Patients Admitted to the Emergency Department for COVID-19: A Case-Control Study

(1) Background: Viral respiratory infections are common triggers for asthma exacerbation, often leading patients to the emergency department (ED). COVID-19, the disease caused by the SARS-CoV-2 virus, typically presents with respiratory symptoms, from minor symptoms, up to and including severe acute respiratory failure. Data on the association between asthma and COVID-19 are conflicting, and those from an ED setting are scarce. Our aims were to assess the prevalence and outcome of patients with asthma admitted to the ED for COVID-19. (2) Methods: We performed a case-control study, extracting data from a registry of adult patients with confirmed COVID-19 consecutively admitted to the ED of our hospital between March 2020 and January 2021. (3) Results: We identified 83 patients with asthma out of 935 individuals (prevalence 8.9%). There were no significant differences between cases and controls regarding both the proportion of hospital admissions and patients with critical COVID-19. (OR 1.37;95% CI 0.52-3.56;and (OR 0.74;95% CI 0.31-1.78 respectively). (4) Conclusions: In patients admitted to the ED for COVID-19, the prevalence of asthma was not higher than expected, and asthma was not associated with a worse outcome, in terms of the rate of hospitalization and critical COVID-19 disease.

Gastrointestinal Involvement in Extra-Digestive Disease: Which Is the Role of Fecal Calprotectin?

Fecal calprotectin (FC) is a very sensitive marker of inflammation of the gastrointestinal tract. Its clinical utility can be appreciated in both intestinal and extraintestinal diseases. Recent evidence suggests a link between intestinal inflammation and dermatological, rheumatic and neurological diseases. This review focuses on the role of FC in non-gastrointestinal disease, such as rheumatic, dermatologic, neurologic and last but not least SARS-CoV-2 infection.

COVID-19 Pneumonia and Gut Inflammation: The Role of a Mix of Three Probiotic Strains in Reducing Inflammatory Markers and Need for Oxygen Support.

Background: COVID-19 disease, which typically presents with respiratory symptoms, can trigger intestinal inflammation through SARS-CoV-2 replication in the gastrointestinal tract. Supplementation with probiotics may have beneficial effects on gut inflammation due to their analgesic and anti-inflammatory properties. The primary objective of our study was to evaluate the efficacy of a mix of three probiotic strains (Bifidobacterium lactis LA 304, Lactobacillus salivarius LA 302, and Lactobacillus acidophilus LA 201; Lactibiane Iki®) in the reduction in fecal calprotectin in patients with COVID-19 pneumonia, compared to a control group. The secondary aim was to evaluate the reduction in oxygen support and length of hospital stay in patients taking the probiotic mix. Patients and Methods: We conducted a prospective randomized controlled trial at Fondazione Policlinico Gemelli, Rome. We enrolled patients with COVID-19 interstitial pneumonia. One group received the probiotic mix twice a day for 10 days in addition to the standard COVID-19 therapy, and a second group received standard COVID-19 therapy without probiotics. We administered oxygen support (through Ventimask or Optiflow®) on days (D) 1, 3, 5, 7 and 10, and the level of fecal calprotectin between D3-D5 and D7-D10. Results: A total of 80 patients (44 M/36 F; mean age: 59.8 ± 17.3) were enrolled with a mean value of calprotectin at enrollment of 140 mg/dl. At D7-10, the probiotic group showed a 35% decrease in fecal calprotectin compared to 16% in the control group, a decrease in C-reactive protein (CRP) of 72.7% compared to 62%, and a slight but not significant decrease in oxygen support compared to the control group. Conclusion: Supplementation with a mix of probiotics for 10 days in patients with COVID-19 interstitial pneumonia significantly reduces inflammatory markers.

Microbiome in Critical Care: An Unconventional and Unknown Ally.

BACKGROUND: The digestive tract represents an interface between the external environment and the body where the interaction of a complex polymicrobial ecology has an important influence on health and disease. The physiological mechanisms that are altered during hospitalization and in the intensive care unit (ICU) contribute to the pathobiota's growth. Intestinal dysbiosis occurs within hours of being admitted to ICU. This may be due to different factors, such as alterations of normal intestinal transit, administration of various medications, or alterations in the intestinal wall, which causes a cascade of events that will lead to the increase of nitrates and decrease of oxygen concentration, and the liberation of free radicals. OBJECTIVE: This work aims to report the latest updates on the microbiota's contribution to developing sepsis in patients in the ICU department. In this short review, the latest scientific findings on the mechanisms of intestinal immune defenses performed both locally and systemically have been reviewed. Additionally, we considered it necessary to review the literature on the basis of the many studies carried out on the microbiota in the critically ill as a prevention to the spread of the infection in these patients. MATERIALS AND METHODS: This review has been written to answer four main questions: 1- What are the main intestinal flora's defense mechanisms that help us to prevent the risk of developing systemic diseases? 2- What are the main Systemic Abnormalities of Dysbiosis? 3- What are the Modern Strategies Used in ICU to Prevent the Infection Spreading? 4- What is the Relationship between COVID-19 and Microbiota? We reviewed 72 articles using the combination of following keywords: "microbiota" and "microbiota" and "intensive care", "intensive care" and "gut", "critical illness", "microbiota" and "critical care", "microbiota" and "sepsis", "microbiota" and "infection", and "gastrointestinal immunity" in: Cochrane Controlled Trials Register, Cochrane Library, Medline and Pubmed, Google Scholar, Ovid/Wiley. Moreover, we also consulted the site ClinicalTrials.com to find out studies that have been recently conducted or are currently ongoing. RESULTS: The critical illness can alter intestinal bacterial flora leading to homeostasis disequilibrium. Despite numerous mechanisms, such as epithelial cells with calciform cells that together build a mechanical barrier for pathogenic bacteria, the presence of mucous associated lymphoid tissue (MALT) which stimulates an immune response through the production of interferon-gamma (IFN-y) and THN-a or or from the production of anti-inflammatory cytokines produced by lymphocytes Thelper 2. But these defenses can be altered following hospitalization in ICU and lead to serious complications, such as acute respiratory distress syndrome (ARDS), health care associated pneumonia (HAP) and ventilator associated pneumonia (VAP), systemic infection and multiple organ failure (MOF), but also to the development of coronary artery disease (CAD). In addition, the microbiota has a significant impact on the development of intestinal complications and the severity of the SARS-COVID-19 patients. CONCLUSION: The microbiota is recognized as one of the important factors that can worsen the clinical conditions of patients who are already very frail in the intensive care unit. At the same time, the microbiota also plays a crucial role in the prevention of ICU-associated complications. By using the resources that are available, such as probiotics, synbiotics or fecal microbiota transplantation (FMT), we can preserve the integrity of the microbiota and the GUT, which will later help maintain homeostasis in ICU patients.

Factors Associated with ICU Admission in Patients with COVID-19: The GOL2DS Score.

Background and Objectives: The COVID-19 pandemic has been shaking lives around the world for nearly two years. The discovery of highly effective vaccines has not been able to stop the transmission of the virus. SARS-CoV-2 shows completely different clinical manifestations. A large percentage (about 40%) of admitted patients require treatment in an intensive care unit (ICU). This study investigates the factors associated with admission of COVID-19 patients to the ICU and whether it is possible to obtain a score that can help the emergency physician to select the hospital ward. Materials and Methods: We retrospectively recorded 313 consecutive patients who were presented to the emergency department (ED) of our hospital and had a diagnosis of COVID-19 confirmed by polymerase chain reaction (PCR) on an oropharyngeal swab. We used multiple logistic regression to evaluate demographic, clinical, and laboratory data statistically associated with ICU admission. These variables were used to create a prognostic score for ICU admission. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver-operating characteristic curve (ROC) of the score for predicting ICU admission during hospitalization were calculated. Results: Of the variables evaluated, only blood type A (p = 0.003), PaO2/FiO2 (p = 0.002), LDH (p = 0.004), lactate (p = 0.03), dyspnea (p = 0.03) and SpO2 (p = 0.0228) were significantly associated with ICU admission after adjusting for sex, age and comorbidity using multiple logistic regression analysis. We used these variables to create a prognostic score called GOL2DS (group A, PaO2/FiO2, LDH, lactate and dyspnea, and SpO2), which had high accuracy in predicting ICU admission (AUROC 0.830 [95% CI, 0.791-0.892). Conclusions: In our single-center experience, the GOL2DS score could be useful in identifying patients at high risk for ICU admission.

Lock, Stock and Barrel: Role of Renin-Angiotensin-Aldosterone System in Coronavirus Disease 2019.

Since the end of 2019, the medical-scientific community has been facing a terrible pandemic caused by a new airborne viral agent known as SARS-CoV2. Already in the early stages of the pandemic, following the discovery that the virus uses the ACE2 cell receptor as a molecular target to infect the cells of our body, it was hypothesized that the renin-angiotensin-aldosterone system was involved in the pathogenesis of the disease. Since then, numerous studies have been published on the subject, but the exact role of the renin-angiotensin-aldosterone system in the pathogenesis of COVID-19 is still a matter of debate. RAAS represents an important protagonist in the pathogenesis of COVID-19, providing the virus with the receptor of entry into host cells and determining its organotropism. Furthermore, following infection, the virus is able to cause an increase in plasma ACE2 activity, compromising the normal function of the RAAS. This dysfunction could contribute to the establishment of the thrombo-inflammatory state characteristic of severe forms of COVID-19. Drugs targeting RAAS represent promising therapeutic options for COVID-19 sufferers.

Effect of influenza vaccine on COVID-19 mortality: a retrospective study.

It has been proposed that vaccines may exert an unspecific protective effect against infectious agents, different than expected. Coronavirus disease 2019 (COVID-19) is a pandemic infection with high mortality in older patients due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The high number of vaccinations may be one of the reasons why children show a lower susceptibility to SARS-CoV-2 infection and milder severity when compared to adults. We have designed a study aimed at investigating whether the influenza vaccine may reduce the susceptibility and severity of SARS-CoV-2 infection. We retrospectively enrolled 635 patients who accessed our Emergency Department from March 1st to June 30th, 2020, and were diagnosed with COVID-19 infection confirmed by an RT-PCR on an oropharyngeal swab. Clinical data, outcomes, and influenza vaccination status were collected from the electronic medical records of our Hospital. We also used data from the Italian Health Ministry to compare the prevalence of flu vaccination among the general population of the Lazio Region and our enrolled patients. We then compared clinical outcomes between vaccinated and non-vaccinated patients, by univariate and multivariate analysis. COVID-19-positive patients older than 65 years reported a lower prevalence of flu vaccination when compared to the general population residing in the Lazio (p = 0.004). After correction for gender, age, and comorbidities, we found a lower risk of death at 60 days in patients with flu vaccination than in not vaccinated patients (p = 0.001). Our study shows that flu vaccination could reduce the mortality of COVID-19. Prospective studies are needed to confirm this result.

Non-COVID Diseases during the Pandemic: Where Have All Other Emergencies Gone?

Background and objectives: the emergency department (ED) is frequently identified by patients as a possible solution for all healthcare problems, leading to a high rate of misuse of the ED, possibly causing overcrowding. The coronavirus disease 2019 (COVID-19) pandemic started in China; it then spread throughout Italy, with the first cases confirmed in Lombardy, Italy, in February 2020. This has totally changed the type of patients referred to EDs. The aim of this study was to analyze the reduction of ED admissions at a Second level urban teaching (Fondazione Policlinico Universitario Agostino Gemelli IRCCS) during the COVID-19 pandemic. Materials and Methods: in this retrospective observational cross-sectional study, we reviewed and compared clinical records of all the patients consecutively admitted to our ED over a 40-day period (21 February -31 March) in the last three years (2018-2019-2020). Mean age, sex, triage urgency level, day/night admission, main presentation symptom, and final diagnosis, according to different medical specialties, hospitalization, and discharge rate, were analyzed. Results: we analyzed 16,281 patient clinical records. The overall reduction in ED admissions in 2020 was 37.6% compared to 2019. In 2020, we observed an increase in triage urgency levels for ED admissions (the main presentation symptom was a fever). We noticed a significant drop in admissions for cardio-thoracic, gastroenterological, urological, otolaryngologic/ophthalmologic, and traumatological diseases. Acute neurological conditions registered only a slight, but significant, reduction. Oncology admissions were stable. Admissions for infectious diseases were 30% in 2020, compared to 5% and 6% in 2018 and 2019, respectively. In 2020, the hospitalization rate increased to 42.9% compared to 27.7%, and 26.4% in previous years. Conclusions: the drastic reduction of ED admissions during the pandemic may be associated with fear of the virus, suggesting that patients with serious illnesses did not go to the emergency room. Moreover, there was possible misuse of the ED in the previous year. In particular, worrisome data emerged regarding a drop in cardiology and neurology admissions. Those patients postponed medical attention, possibly with fatal consequences, just for fear of exposure to COVID-19, leading to unnecessary morbidity and mortality.

Predicting intensive care unit admission and death for COVID-19 patients in the emergency department using early warning scores.

AIMS: To identify the most accurate early warning score (EWS) for predicting an adverse outcome in COVID-19 patients admitted to the emergency department (ED). METHODS: In adult consecutive patients admitted (March 1-April 15, 2020) to the ED of a major referral centre for COVID-19, we retrospectively calculated NEWS, NEWS2, NEWS-C, MEWS, qSOFA, and REMS from physiological variables measured on arrival. Sensitivity, specificity, positive (PPV) and negative predictive value (NPV), and the area under the receiver operating characteristic (AUROC) curve of each EWS for predicting admission to the intensive care unit (ICU) and death at 48 h and 7 days were calculated. RESULTS: We included 334 patients (119 [35.6%] females, median age 66 [54-78] years). At 7 days, the rates of ICU admission and death were 56/334 (17%) and 26/334 (7.8%), respectively. NEWS was the most accurate predictor of ICU admission within 7 days (AUROC 0.783 [95% CI, 0.735-0.826]; sensitivity 71.4 [57.8-82.7]%; NPV 93.1 [89.8-95.3]%), while REMS was the most accurate predictor of death within 7 days (AUROC 0.823 [0.778-0.863]; sensitivity 96.1 [80.4-99.9]%; NPV 99.4[96.2-99.9]%). Similar results were observed for ICU admission and death at 48 h. NEWS and REMS were as accurate as the triage system used in our ED. MEWS and qSOFA had the lowest overall accuracy for both outcomes. CONCLUSION: In our single-centre cohort of COVID-19 patients, NEWS and REMS measured on ED arrival were the most sensitive predictors of 7-day ICU admission or death. EWS could be useful to identify patients with low risk of clinical deterioration.

Clinical characteristics and prognostic factors in COVID-19 patients aged ≥80 years.

AIM: The aim of the present study was to describe the clinical presentation of patients aged ≥80 years with coronavirus disease 2019 (COVID-19), and provide insights regarding the prognostic factors and the risk stratification in this population. METHODS: This was a single-center, retrospective, observational study, carried out in a referral center for COVID-19 in central Italy. We reviewed the clinical records of patients consecutively admitted for confirmed COVID-19 over a 1-month period (1-31 March 2020). We excluded asymptomatic discharged patients. We identified risk factors for death, by a uni- and multivariate Cox regression analysis. To improve model fitting and hazard estimation, continuous parameters where dichotomized by using Youden's index. RESULTS: Overall, 69 patients, aged 80-98 years, met the inclusion criteria and were included in the study cohort. The median age was 84 years (82-89 years is interquartile range); 37 patients (53.6%) were men. Globally, 14 patients (20.3%) presented a mild, 30 (43.5%) a severe and 25 (36.2%) a critical COVID-19 disease. A total of 23 (33.3%) patients had died at 30 days' follow up. Multivariate Cox regression analysis showed that severe dementia, pO2 ≤90 at admission and lactate dehydrogenase >464 U/L were independent risk factors for death. CONCLUSIONS: The present data suggest that risk of death could be not age dependent in patients aged ≥80 years, whereas severe dementia emerged is a relevant risk factor in this population. Severe COVID-19, as expressed by elevated lactate dehydrogenase and low oxygen saturation at emergency department admission, is associated with a rapid progression to death in these patients. Geriatr Gerontol Int 2020; ••: ••-••.