Serum lipid mediator profiles in COVID-19 patients and lung disease severity: a pilot study.

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection is highly heterogeneous, ranging from asymptomatic to severe and fatal cases. COVID-19 has been characterized by an increase of serum pro-inflammatory cytokine levels which seems to be associated with fatal cases. By contrast, the role of pro-resolving lipid mediators (SPMs), involved in the attenuation of inflammatory responses, has been scarcely investigated, so further studies are needed to understand SPMs metabolism in COVID-19 and other infectious diseases. Our aim was to analyse the lipid mediator metabolome, quantifying pro- and anti-inflammatory serum bioactive lipids by LC-MS/MS in 7 non-infected subjects and 24 COVID-19 patients divided into mild, moderate, and severe groups according to the pulmonary involvement, to better understand the disease outcome and the severity of the pulmonary manifestations. Statistical analysis was performed with the R programming language (R Foundation for Statistical Computing, Vienna, Austria). All COVID-19 patients had increased levels of Prostaglandin E2. Severe patients showed a significant increase versus controls, mild- and moderate-affected patients, expressed as median (interquartile range), in resolvin E1 [112.6 (502.7) vs 0.0 (0.0) pg/ml in the other groups], as well as in maresin 2 [14.5 (7.0) vs 8.1 (4.2), 5.5 (4.3), and 3.0 (4.0) pg/ml, respectively]. Moreover, 14-hydroxy docosahexaenoic acid (14-HDHA) levels were also increased in severe vs control and mild-affected patients [24.7 (38.2) vs 2.4 (2.2) and 3.7 (6.4) ng/mL, respectively]. Resolvin D5 was also significantly elevated in both moderate [15.0 (22.4) pg/ml] and severe patients [24.0 (24.1) pg/ml] versus controls [0.0 (0.0) pg/ml]. These results were confirmed by sparse partial least squares discriminant analysis which highlighted the contribution of these mediators to the separation between each of the groups. In conclusion, the potent inflammatory response to SARS-CoV-2 infection involves not only pro- but also anti-inflammatory lipid mediators that can be quantified in easily accessible serum samples, suggesting the need to perform future research on their generation pathways that will help us to discover new therapeutic targets.

A Point-of-Care Faecal Test Combining Four Biomarkers Allows Avoidance of Normal Colonoscopies and Prioritizes Symptomatic Patients with a High Risk of Colorectal Cancer.

Most colonoscopies performed to evaluate gastrointestinal symptoms detect only non-relevant pathologies. We aimed to evaluate the diagnostic accuracy of a qualitative point-of-care (POC) test combining four biomarkers (haemoglobin, transferrin, calprotectin, and lactoferrin), a quantitative faecal immunochemical test (FIT) for haemoglobin, and a quantitative faecal calprotectin (FC) test in symptomatic patients prospectively recruited. Colorectal cancer (CRC), adenoma requiring surveillance, inflammatory bowel disease (IBD), microscopic colitis, and angiodysplasia were considered significant pathologies. A total of 571 patients were included. Significant pathology was diagnosed in 118 (20.7%), including 30 CRC cases (5.3%). The POC test yielded the highest negative predictive values: 94.8% for a significant pathology and 100% for CRC or IBD if the four markers turned negative (36.8% of the patients). Negative predictive values of FIT, FC, and its combination for diagnosis of a significant pathology were 88.4%, 87.6%, and 90.8%, respectively. Moreover, the positive predictive value using the POC test was 82.3% for significant pathology when all biomarkers tested positive (6% of the patients), with 70.6% of these patients diagnosed with CRC or IBD. The AUC of the POC test was 0.801 (95%CI 0.754-0.848) for the diagnosis of a significant pathology. Therefore, this POC faecal test allows the avoidance of unnecessary colonoscopies and prioritizes high risk symptomatic patients.

Impact of the COVID-19 pandemic in colorectal cancer diagnosis and presentation.

BACKGROUND AND OBJECTIVE: The COVID-19 pandemic has been associated with a decrease in the colorectal cancer (CRC) incidence, due to the disruption of screening programmes and a downscaling of endoscopic activity. The endpoint of this study is to evaluate if the pandemic has led to a change in CRC diagnostic rate and presentation in our population. METHODS: Multicenter retrospective study of all public hospitals of the Aragon region, attending a population of 1,329,391 inhabitants. We have analyzed all CRC cases detected and endoscopic units workload the year before the pandemic onset (1 March 2019-14 March 2020) and the first year of the COVID-19 pandemic (15 March 2020-28 February 2021). RESULTS: The diagnosis of CRC cases dropped a 38.9% (888 pre-pandemic vs 542 pandemic cases). Also, there were 30.3% less colonoscopies performed (24,860 vs 17,337). During the pandemic, CRC cases were diagnosed in older patients (72.4±12.2 vs 71.2±12.1 years, p=0.021), and had more frequently severe complications at diagnosis (14.6% vs 10.4%, p=0.019). Moreover, most CRC cases were diagnosed in symptomatic patients (81.4%). No significant difference was found in CRC stage at diagnosis, although stage IV was more frequent (20.1% vs 16.1%). Most hospitals reported a lower workload of endoscopic activity. CONCLUSION: CRC diagnostic rate was lower after the onset of the pandemic. CRC was diagnosed in older patients and was more frequently associated with complications. After the onset of the pandemic, the endoscopic units did not reach the workload performed previously.

The impact of COVID-19 pandemic in the diagnosis and management of colorectal cancer patients.

The novel coronavirus disease 2019 (COVID-19) pandemic has posed an unprecedented challenge to healthcare systems worldwide, causing downscaling of almost all other activities, especially in its early stages. Currently, the availability of vaccines along with the spread of new viral variants has modified the epidemiology of the disease, and the previous activity is being gradually resumed in most healthcare facilities. In this review, we have summarized the influence of the COVID-19 pandemic in the diagnosis and management of colorectal cancer (CRC) patients. Population-based screening with either colonoscopy or fecal occult blood tests has proven to reduce CRC incidence and mortality, so screening programs have been implemented in most western countries. However, during the first COVID-19 wave, most of these programs had to be disrupted temporarily. In this review, we have thoroughly analyzed the consequences of these disruptions of screening programs as well as of the forced delays in diagnostic and therapeutic services on CRC prognosis, although its exact impact cannot be exactly measured yet. In any way, strategies to minimize its effect, such as catch-up strategies expanding the colonoscopy capacity or using fecal occult blood concentration and other risk factors to prioritize patients, are urgently needed. The COVID-19 pandemic has also led to a change in CRC patient presentation, with an overall temporary decreased incidence due to postponed diagnoses, but with more patients presenting in need of an emergency admission or with symptoms. Finally, changes in treatment approaches in CRC patients have been reported during the pandemic, namely a drop in the proportion of laparoscopic surgeries or a rise in short-term radiotherapy courses. We have therefore aimed to summarize the available evidence to guide the healthcare professionals treating CRC patients to choose the best treatment options in the current pandemic situation.

A Patient Self-Made Point-of-Care Fecal Test Improves Diagnostic Accuracy Compared with Fecal Calprotectin Alone in Inflammatory Bowel Disease Patients.

BACKGROUND: Monitoring inflammatory bowel disease patients may be challenging. Fecal calprotectin is one of the most performed tests. Other fecal biomarkers are less used in clinical practice. Rapid fecal tests that could be performed by patients may be a useful strategy to closely monitor disease activity. METHODS: We performed a prospective observational study including consecutive inflammatory bowel disease patients referred for colonoscopy in a single center. Certest FOB + Transferrin + Calprotectin + Lactoferrin® (Certest Biotec S.L, Zaragoza, Spain), a one-step point-of-care test which simultaneously detects these four biomarkers was performed. Endoscopic inflammatory activity was defined using the Mayo score (≥1) in ulcerative colitis, SES-CD (>3) and Rutgeerts scores (≥1) for Crohn's disease. RESULTS: Out of a total of 106 patients (56.5% female, mean age 51 years), 54 (50.9%) were diagnosed with ulcerative colitis and 52 (49.1%) with Crohn's disease. Endoscopic activity was detected in 42 patients (39.0%). Fecal calprotectin provided the best sensitivity (97.6%), with limited specificity (34.4%). Compared to calprotectin, the other 3 fecal biomarkers showed better specificity (87.5-92.1%) and lower sensitivity (45.2-59.5%). Patients with a negative result in all biomarkers (19/106-17.9%) had 100% (CI 95% 97.4-100) negative predictive value, while patients with the 4 biomarkers positive (13/106-12.3%) had 100% (CI 95% 96.1-100) positive predictive value of endoscopic inflammatory activity. AUROC of this 4 biomarker point-of-care test was 0.845 (95% CI 0.771-0.920), significantly higher than the AUROCs of any of the 4 biomarkers. CONCLUSIONS: This test may be a useful strategy to monitor inflammatory activity in clinical practice by excluding or prioritizing patients in need of a colonoscopy.

Changes in severity, mortality, and virus genome among a Spanish cohort of patients hospitalized with SARS-CoV-2.

Comparing pandemic waves could aid in understanding the evolution of COVID-19. The objective of the present study was to compare the characteristics and outcomes of patients hospitalized for COVID-19 in different pandemic waves in terms of severity and mortality. We performed an observational retrospective cohort study of 5,220 patients hospitalized with SARS-CoV-2 infection from February to September 2020 in Aragon, Spain. We compared ICU admissions and 30-day mortality, clinical characteristics, and risk factors of the first and second waves of COVID-19. The SARS-CoV-2 genome was also analyzed in 236 samples. Patients in the first wave (n = 2,547) were older (median age 74 years [IQR 60-86] vs. 70 years [53-85]; p < 0.001) and had worse clinical and analytical parameters related to severe COVID-19 than patients in the second wave (n = 2,673). The probability of ICU admission at 30 days was 16% and 10% (p < 0.001) and the cumulative 30-day mortality rates 38% and 32% in the first and second wave, respectively (p = 0.007). Survival differences were observed among patients aged 60 to 80 years. We also found some variability among death risk factors and the viral genome between waves. Therefore, the two analyzed COVID-19 pandemic waves were different in terms of disease severity and mortality.

A Clinical Decision Web to Predict ICU Admission or Death for Patients Hospitalised with COVID-19 Using Machine Learning Algorithms.

The purpose of the study was to build a predictive model for estimating the risk of ICU admission or mortality among patients hospitalized with COVID-19 and provide a user-friendly tool to assist clinicians in the decision-making process. The study cohort comprised 3623 patients with confirmed COVID-19 who were hospitalized in the SALUD hospital network of Aragon (Spain), which includes 23 hospitals, between February 2020 and January 2021, a period that includes several pandemic waves. Up to 165 variables were analysed, including demographics, comorbidity, chronic drugs, vital signs, and laboratory data. To build the predictive models, different techniques and machine learning (ML) algorithms were explored: multilayer perceptron, random forest, and extreme gradient boosting (XGBoost). A reduction dimensionality procedure was used to minimize the features to 20, ensuring feasible use of the tool in practice. Our model was validated both internally and externally. We also assessed its calibration and provide an analysis of the optimal cut-off points depending on the metric to be optimized. The best performing algorithm was XGBoost. The final model achieved good discrimination for the external validation set (AUC = 0.821, 95% CI 0.787-0.854) and accurate calibration (slope = 1, intercept = -0.12). A cut-off of 0.4 provides a sensitivity and specificity of 0.71 and 0.78, respectively. In conclusion, we built a risk prediction model from a large amount of data from several pandemic waves, which had good calibration and discrimination ability. We also created a user-friendly web application that can aid rapid decision-making in clinical practice.

Evidence-Based Selection on the Appropriate FIT Cut-Off Point in CRC Screening Programs in the COVID Pandemic.

Background: The COVID pandemic has forced the closure of many colorectal cancer (CRC) screening programs. Resuming these programs is a priority, but fewer colonoscopies may be available. We developed an evidence-based tool for decision-making in CRC screening programs, based on a fecal hemoglobin immunological test (FIT), to optimize the strategy for screening a population for CRC. Methods: We retrospectively analyzed data collected at a regional CRC screening program between February/2014 and November/2018. We investigated two different scenarios: not modifying vs. modifying the FIT cut-off value. We estimated program outcomes in the two scenarios by evaluating the numbers of cancers and adenomas missed or not diagnosed in due time (delayed). Results: The current FIT cut-off (20-µg hemoglobin/g feces) led to 6,606 colonoscopies per 100,000 people invited annually. Without modifying this FIT cut-off value, when the optimal number of individuals invited for colonoscopies was reduced by 10-40%, a high number of CRCs and high-risk adenomas (34-135 and 73-288/100.000-people invited, respectively) will be undetected every year. When the FIT cut-off value was increased to where the colonoscopy demand matched the colonoscopy availability, the number of missed lesions per year was remarkably reduced (9-36 and 29-145/100.000 people, respectively). Moreover, the unmodified FIT scenario outcome was improved by prioritizing the selection process based on sex (males) and age, rather than randomly reducing the number invited. Conclusions: Assuming a mismatch between the availability and demand for annual colonoscopies, increasing the FIT cut-off point was more effective than randomly reducing the number of people invited. Using specific risk factors to prioritize access to colonoscopies should be also considered.

COVID-19 and Gastrointestinal Disease: Implications for the Gastroenterologist.

BACKGROUND: COVID-19 was initially considered a respiratory disease but the SARS-CoV-2 virus can lead to serious systemic consequences affecting major organs including the digestive system. SUMMARY: This review brings new clinically important information for the gastroenterologist. This includes: the mechanisms of tissue damage seen with the SARS-CoV-2 virus; the consequences of immunosuppression in patients with inflammatory bowel disease (IBD) and chronic liver disease with the additional risks of decompensation in patients with cirrhosis; the impact of COVID-19 on gastrointestinal emergencies, on gastrointestinal endoscopy, diagnosis and treatments. These highlight the need to understand the clinical pharmacology, toxicology and therapeutic implications of drugs commonly used by gastroenterologists and their links with COVID-19. Key Messages: Any part of the digestive system may be affected by the SARS-CoV-2 virus, and those with pre-existing disease are at greatest risk of adverse outcomes. The risk for drug-drug interactions is considerable in patients seriously ill with COVID-19 who often require mechanical ventilation and life support. Some repurposed drugs used against SARS-CoV-2 can cause or aggravate some of the COVID-19-related gastrointestinal symptoms and can also induce liver injury. Ongoing clinical studies will hopefully identify effective drugs with a more favourable risk-benefit ratio than many initially tried treatments.