Antimicrobial peptides: Defending the mucosal epithelial barrier.

The recent epidemic caused by aerosolized SARS-CoV-2 virus illustrates the importance and vulnerability of the mucosal epithelial barrier against infection. Antimicrobial proteins and peptides (AMPs) are key to the epithelial barrier, providing immunity against microbes. In primitive life forms, AMPs protect the integument and the gut against pathogenic microbes. AMPs have also evolved in humans and other mammals to enhance newer, complex innate and adaptive immunity to favor the persistence of commensals over pathogenic microbes. The canonical AMPs are helictical peptides that form lethal pores in microbial membranes. In higher life forms, this type of AMP is exemplified by the defensin family of AMPs. In epithelial tissues, defensins, and calprotectin (complex of S100A8 and S100A9) have evolved to work cooperatively. The mechanisms of action differ. Unlike defensins, calprotectin sequesters essential trace metals from microbes, which inhibits growth. This review focuses on defensins and calprotectin as AMPs that appear to work cooperatively to fortify the epithelial barrier against infection. The antimicrobial spectrum is broad with overlap between the two AMPs. In mice, experimental models highlight the contribution of both AMPs to candidiasis as a fungal infection and periodontitis resulting from bacterial dysbiosis. These AMPs appear to contribute to innate immunity in humans, protecting the commensal microflora and restricting the emergence of pathobionts and pathogens. A striking example in human innate immunity is that elevated serum calprotectin protects against neonatal sepsis. Calprotectin is also remarkable because of functional differences when localized in epithelial and neutrophil cytoplasm or released into the extracellular environment. In the cytoplasm, calprotectin appears to protect against invasive pathogens. Extracellularly, calprotectin can engage pathogen-recognition receptors to activate innate immune and proinflammatory mechanisms. In inflamed epithelial and other tissue spaces, calprotectin, DNA, and histones are released from degranulated neutrophils to form insoluble antimicrobial barriers termed neutrophil extracellular traps. Hence, calprotectin and other AMPs use several strategies to provide microbial control and stimulate innate immunity.

Serum calprotectin can indicate current and future severity of COVID-19.

BACKGROUND: Predictive and prognostic biomarkers to guide 2019 novel coronavirus disease (COVID-19) are critically evolving. Dysregulated immune responses are the pivotal cause of severity mainly mediated by neutrophil activation. Thus, we evaluated the association of calprotectin, neutrophil secretory protein, and other mediators of inflammation with the severity and outcomes of COVID-19. METHODS: This two-center prospective study focused on PCR-proven COVID-19 patients (n = 76) with different clinical presentations and SARS-CoV-2 negative control subjects (n = 24). Serum calprotectin (SC) was compared with IL-6 and other laboratory parameters. RESULTS: Median levels of SC were significantly higher in COVID-19 patients in comparison to the control group (3760 vs. 2100 ng/ml, p < 0.0001). Elevated SC was significantly respective of disease severity (3760 ng/ml in mild up to 5700 ng/ml in severe cases, p < 0.0001). Moreover, the significant positive and negative correlations of SC with disease severity and oxygenation status indicated disease progression and respiratory worsening, respectively. It was found that SC was high in severe patients during hospitalization and significantly declined to normal after recovery. The logistic analysis identified the independent predictive power of SC for respiratory status or clinical severity. Indeed, SC behaved as a better discriminator for both outcomes, as it exhibited the largest area under the curve (receiver operating curve analysis), with the highest specificity and sensitivity when the predictive value of inflammatory biomarkers was compared. CONCLUSION: Calprotectin can be used as a reliable prognostic tool to predict the poor clinical outcomes of COVID-19 patients.

Hepatobiliary system and intestinal injury in new coronavirus infection (COVID-19): A retrospective study.

BACKGROUND: An important area of effective control of the coronavirus disease 19 (COVID-19) pandemic is the study of the pathogenic features of severe acute respiratory syndrome coronavirus 2 infection, including those based on assessing the state of the intestinal microbiota and permeability. AIM: To study the clinical features of the new COVID-19 in patients with mild and moderate severity at the stage of hospitalization, to determine the role of hepatobiliary injury, intestinal permeability disorders, and changes in the qualitative and quantitative composition of the microbiota in the development of systemic inflammation in patients with COVID-19. METHODS: The study was performed in 80 patients with COVID-19, with an average age of 45 years, 19 of whom had mild disease, and 61 had moderate disease severity. The scope of the examination included traditional clinical, laboratory, biochemical, instrumental, and radiation studies, as well as original methods for studying microbiota and intestinal permeability. RESULTS: The clinical course of COVID-19 was studied, and the clinical and biochemical features, manifestations of systemic inflammation, and intestinal microbiome changes in patients with mild and moderate severity were identified. Intestinal permeability characteristics against the background of COVID-19 were evaluated by measuring levels of proinflammatory cytokines, insulin, faecal calprotectin, and zonulin. CONCLUSION: This study highlights the role of intestinal permeability and microbiota as the main drivers of gastroenterological manifestations and increased COVID-19 severity.

At Home Calprotectin a United Kingdom Patient Perspectives and Tertiary Center Experience

Background: Home faecal calprotectin tests (HFCT) have been available for some years with slow uptake to use in the UK. During the Sars-Cov-2 pandemic use increased as it allowed a measure of disease activity when lab testing in some areas ceased. In a United Kingdom tertiary referral IBD unit, CalproSmart was introduced in 2020. We analysed completion rates of HFCT and the barriers and enablers patients experienced in its use. Method(s): Data from the CalproSmart portal was analysed. Total patients registered was compared against the number that had completed a test. Age, sex and return rates per annum as well as local or out of area patients were included. All patients who enrolled to receive a HFCT were sent an anonymous online questionnaire using MS Forms. Descriptive statistics were used to analysis the results with a thematic analysis of free form text answers. Result(s): A total of N=304 patients were enrolled on the CalproSmart portal over a three-year period from October 2020 until July 2021. HFCT was completed by 118 (39%) of these patients. Completion was highest in 2020 78% of patients who enrolled on the system completed a HFCT. There was a slight trend towards females being more likely to complete at 23% versus 16% of males. There was no sign of age as a determinant to completion. Of the 118 patients who completed the HFCT 84 (71%) were out of local area patients and 34 (29%) local patients. There were 54 (17%) questionnaires returned. All but 4 (7%) respondents had attempted or completed the HFCT. When asked why they wanted to try a HFCT 39 (72%) patients indicated not having to go to hospital/GP as their primary reason with getting an instant result 29 (54%) and seeing your own result 27 (50%) coming in next. 13 (24%) cited more disease control as a reason to try the test. People found the test mostly easy to use but when comparing overall happiness with the HFCT kits 9 people reported they were somewhat unhappy or unhappy. People were either happy or unhappy with the HFC test usability is a theme that is generated as a barrier and a facilitator for some (see figure 1). When asked which they would prefer to do in future CalproSmart at home or bring your sample to either your GP or hospital n=45 (83%) preferred HFCT. Figure 1 Q 12 Overall how happy were you with CalproSmart home calprotectin kit? Free text answer comparison Conclusion(s): During the pandemic HFCT were popular and out of area patients were more likely to complete the kits. Despite the low return rates those that chose to complete HFCT were in most of cases happy to continue HFCT. With, attention to patient selection and enhanced training on the HFCT there is a case for the continued use in services that have altered significantly since the pandemic. (Figure Presented).

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.

Faecal calprotectin in COVID-19 patients with intestinal symptoms.

Introduction: Extra-pulmonary manifestations of the Coronavirus disease of 2019 (COVID-19) have been increasingly reported, especially gastrointestinal and hepatic system dysfunction. The concern of faecal-oral transmission for COVID-19 was raised. Aim: To study the trend of faecal calprotectin in COVID-19 patients with intestinal symptoms. Material and methods: Forty confirmed cases of COVID-19 infection presenting with diarrhoea were subjected to a thorough history taking, clinical examination, and routine laboratory investigations. They were treated according to the Egyptian MOH guidelines. Faecal calprotectin (FC) concentration was measured at initial presentation and after 3 months. Those who had persistently elevated levels ≥ 200 µg/g were subjected to colonoscopic examination and histopathological examination. Forty confirmed cases of COVID-19 without diarrhoea were recruited as a control group in the initial FC evaluation. Results: Faecal calprotectin was found to be significantly elevated in the studied COVID-19 patients who presented with diarrhoea, with a mean value 260 ±80 µg/g compared to the those without diarrhoea, with a mean value of 31.6 ±12.9 µg/g (p < 0.001). Moreover, 20% (8 patients) had an elevated level exceeding 200 µg/g 3 months after recovery; among them, 5 patients showed mild colonoscopic changes whereas 3 patients showed severe ileocolitis. Out of the 3 patients with marked ileocolitis, 2 showed histopathological changes raising the diagnosis of Crohn's disease. Conclusions: Faecal calprotectin was found to be elevated in COVID-19 patients with intestinal symptoms, especially diarrhoea, with or without colonoscopic and histopathological changes.

Comparison of faecal calprotectin using two collection and extraction strategies for the BÜHLMANN CALEX® Cap - possible implications for clinical cut-offs?

BACKGROUND: Faecal calprotectin has been identified as a useful biochemical marker in the differentiation of inflammatory bowel disease and irritable bowel syndrome. Typically, patients send faecal specimens in a pot for manual extraction by the laboratory. During the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) pandemic, the routine laboratory service was temporarily suspended due to the potential increased risk to staff. In this study we investigated the possibility of patients collecting samples directly into the faecal extraction tubes. METHOD: Patients submitted paired faecal samples for calprotectin analysis using a standard faecal container (current practice) and followed instructions for faecal collection using the BÜHLMANN CALEX® Cap device. Samples were returned to the laboratory immediately after collection. Laboratory staff manually extracted the calprotectin from the faecal samples using the CALEX® Cap prior to analysis of both extracts on the Cobas c702. RESULTS: 91 paired faecal samples were included in the study. Clinical correlation was found to be 70% with numerical correlation showing a positive bias for the patient-collected CALEX® Cap sample when compared to the laboratory-extracted faecal sample around the clinical decision points 100-250 µg calprotectin/g faeces. CONCLUSION: The study shows that collection of a faecal sample using the CALEX® Cap works well and is a good alternative to using standard containers. The correlation gives rise to the possibility that faecal calprotectin is not stable when collected into standard collection containers. Prior to further roll-out of this process, questions surrounding the current cut-offs would need to be addressed.

Serial measurement of circulating calprotectin as a prognostic biomarker in COVID-19 patients in intensive care setting.

OBJECTIVES: Circulating calprotectin (cCLP) has been shown to be a promising prognostic marker for COVID-19 severity. We aimed to investigate the prognostic value of serial measurements of cCLP in COVID-19 patients admitted to an intensive care unit (ICU). METHODS: From November 2020 to May 2021, patients with COVID-19, admitted at the ICU of the OLV Hospital, Aalst, Belgium, were prospectively included. For sixty-six (66) patients, blood samples were collected at admission and subsequently every 48 h during ICU stay. On every sample (total n=301), a cCLP (EliA™ Calprotectin 2, Phadia 200, Thermo Fisher Scientific; serum/plasma protocol (for Research Use Only, -RUO-) and C-reactive protein (CRP; cobas c501/c503, Roche Diagnostics) analysis were performed. Linear mixed models were used to associate biomarkers levels with mortality, need for mechanical ventilation, length of stay at ICU (LOS-ICU) and medication use (antibiotics, corticosteroids, antiviral and immune suppressant/modulatory drugs). RESULTS: Longitudinally higher levels of all biomarkers were associated with LOS-ICU and with the need for mechanical ventilation. Medication use and LOS-ICU were not associated with variations in cCLP and CRP levels. cCLP levels increased significantly during ICU hospitalization in the deceased group (n=21/66) but decreased in the non-deceased group (n=45/66). In contrast, CRP levels decreased non-significantly in both patient groups, although significantly longitudinally higher CRP levels were obtained in the deceased subgroup. CONCLUSIONS: Serial measurements of cCLP provides prognostic information which can be useful to guide clinical management of COVID-19 patients in ICU setting.

Studying and Improving Treatment of Calprotectin, Helicobacter Pylori and Interleukin-6 in Blood of Patients with Covid-19

Of the 100 patients who were followed up, 60 were "relatively cured" of Covid-19 and 40 were uninfected. The levels of calprotectin, Helicobacter pylori and interleukin-6 in the blood, which were detected in their feces, were reliably higher in those who passed the coronavirus. At the next stage of the study, the patients of the first group were divided into 2 subgroups of 30 based on the complex treatments prescribed on the basis of the standard of treatment of the existing disease. The first subgroup was prescribed rebamipide as a combination therapy and compared with the other two groups. In the group that received rebamipide, compared to those that did not receive it, it was found that calprotectin, Helicobacter pylori and interleukin-6 in the blood were significantly reduced. Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

Role of cystatin C and calprotectin as potential early prognostic biomarkers in COVID-19 patients admitted to a dedicated COVID care facility.

Background: The COVID-19 pandemic has claimed millions of lives. A tool for early prediction of severity and mortality risk is desirable for better utilization of health care facilities. Several biomarkers like D-dimer, lactate dehydrogenase (LDH), C-reactive protein (CRP) and some recently explored biomarkers like serum cystatin C and serum calprotectin have been proposed as prognostic markers of COVID-19, but their role as prognostic markers is so far undefined. The present work attempted to investigate the possible role of serum cystatin C and serum calprotectin as prognostic tools to predict severity and outcome ahead of time. Material and Methods: This observational cohort study was carried out on 95 COVID-19 patients admitted to a dedicated COVID care facility from mid-October 2020 to January 2021. Serial estimations of serum cystatin C and serum calprotectin levels were done and assessed for significant difference between severe (NEWS 2 score ≥5) and non-severe (NEWS 2 score <5) groups, survivors and deceased and on the basis of comorbidities at each time points. Survival analysis was done based on the optimal thresholds for severity and mortality, calculated from the receiver operating characteristic (ROC). Result: The results showed that median cystatin C levels were significantly higher on the first day in the severe group (P < 0.001) and in patients with cardiovascular disease (P < 0.05), chronic lung disease (P = 0.009) and among patients who died (P < 0.05). It remained raised on day 3 in severe (P < 0.05) and deceased (P < 0.05) group. Serum calprotectin levels were significantly higher in patients with chronic lung disease (P = 0.008) and in those who died (P < 0.05). Conclusion: Serum cystatin C could be used as a tool for early prognosis and therapeutic decision-making for COVID-19 patients. Serum calprotectin seems to be a better marker of critical illness.

Calprotectin Levels and Neutrophil Count Are Prognostic Markers of Mortality in COVID-19 Patients.

Inflammation plays a crucial role in worsening coronavirus disease (COVID-19). Calprotectin is a pro-inflammatory molecule produced by monocytes and neutrophilic granulocytes. The aim of the study was to evaluate both the prognostic role of circulating calprotectin levels and neutrophil count toward fatal outcome in COVID-19 patients. We retrospectively collected and analyzed data on 195 COVID-19 adult patients, 156 hospitalized in the infectious disease unit and 39 in the intensive care unit (ICU). Calprotectin levels and neutrophil counts measured at the first hospitalization day were higher in the patients with a fatal outcome than in surviving ones. The association of high calprotectin levels and neutrophil count to patient death remain significant by logistic regression, independent of patient age. ROC curves analysis for calprotectin levels and neutrophil count revealed a good discriminatory power toward survival (area under the curve of 0.759 and 0.843, respectively) and identified the best cut-off (1.66 mg/L and 16.39 × 103/µL, respectively). Kaplan-Meier analysis confirmed the prognostic role of high calprotectin levels and neutrophil count in death prediction. In conclusion, this study highlights that calprotectin levels together with neutrophil count should be considered as biomarkers of mortality in COVID-19 patients.

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.

Investigation of hemogram, oxidative stress, and some inflammatory marker levels in neonatal calves with escherichia coli and coronavirus diarrhea.

Calf diarrhea is the most common disease affecting calves in the neonatal period resulting in economic losses. Although predisposing factors play a role in the etiology of the disease, in most cases, different pathogens are involved in the development of the infection. In this study, hemogram data, glutathione and malondialdehyde levels were examined to determine lipid peroxidation and glutathione levels in E. coli- and coronavirus-infected calves. Serum amyloid A and calprotectin levels were also analyzed to determine inflammatory status. The study included a total of 45 female Montofon calves aged 0-1 week, including the E. coli group (15 calves), the coronavirus group (15 calves), and the control group (15 calves). Analysis revealed that total leukocyte, neutrophil, lymphocyte, malondialdehyde, serum amyloid A, and calprotectin levels increased in the coronavirus-infected calves compared with the E. coli group and the control group. In contrast, the levels of glutathione, one of the antioxidant markers, decreased. In conclusion, the main findings related to the determination of inflammation and oxidative status were characterized by the presence of E. coli and coronavirus diarrhea, and it is suggested that future studies may be guided by the fact that inflammatory conditions are higher in viral disease than in bacterial infection.

Dok3 restrains neutrophil production of calprotectin during TLR4 sensing of SARS-CoV-2 spike protein.

Increased neutrophils and elevated level of circulating calprotectin are hallmarks of severe COVID-19 and they contribute to the dysregulated immune responses and cytokine storm in susceptible patients. However, the precise mechanism controlling calprotectin production during SARS-CoV-2 infection remains elusive. In this study, we showed that Dok3 adaptor restrains calprotectin production by neutrophils in response to SARS-CoV-2 spike (S) protein engagement of TLR4. Dok3 recruits SHP-2 to mediate the de-phosphorylation of MyD88 at Y257, thereby attenuating downstream JAK2-STAT3 signaling and calprotectin production. Blocking of TLR4, JAK2 and STAT3 signaling could prevent excessive production of calprotectin by Dok3-/- neutrophils, revealing new targets for potential COVID-19 therapy. As S protein from SARS-CoV-2 Delta and Omicron variants can activate TLR4-driven calprotectin production in Dok3-/- neutrophils, our study suggests that targeting calprotectin production may be an effective strategy to combat severe COVID-19 manifestations associated with these emerging variants.

Inflammatory markers calprotectin, NETs, syndecan-1 and neopterin in COVID-19 convalescent blood donors.

Persisting inflammation has been discovered in lungs and other parenchymatous organs of some COVID-19 convalescents. Calprotectin, neutrophil extracellular traps (NETs), syndecan-1 and neopterin are general key inflammatory markers, and systemically enhanced levels of them may remain after the COVID-19 infection. These inflammatory markers were therefore measured in serum samples of 129 COVID-19 convalescent and 27 healthy blood donors or employees at Oslo Blood bank, Norway. Also antibodies against SARS-CoV-2 nucleocapsid antigen were measured, and timing of sampling and severity of infection noted. Whereas neopterin and NETs values remained low and those for syndecan-1 were not raised to statistically significant level, concentrations for calprotectin, as measured by a novel mixed monoclonal assay, were significantly increased in the convalescents. Antibodies against SARS-CoV-2 nucleocapsid antigen were elevated, but did not correlate with levels of inflammatory markers. Difference between the groups in only one biomarker makes evaluation of ongoing or residual inflammation in the convalescents difficult. If there is a low-grade inflammation, it would in that case involve neutrophils.

Impaired tryptophan metabolism in the gastrointestinal tract of patients with critical coronavirus disease 2019.

Introduction: Coronavirus disease 2019 (COVID-19) is still causing a global pandemic. But the mechanism of COVID-19 severity is not well elucidated. Materials and methods: We conducted two single-center observational studies of patients with COVID-19. In the first study, the enrolled patients were distinguished based on critical vs. non-critical COVID-19. We collected blood samples from the patients at admission to measure markers related to inflammation and thrombosis and stool samples to analyze the fecal microbiome, metabolome, and calprotectin level. In the second study, we collected ileum and colon tissue samples from patients with critical COVID-19 who required colonoscopy due to severe gastrointestinal symptoms and analyzed mucosal gene expression. Results: A total of 19 blood samples and 10 stool samples were collected. Interleukin (IL)-6 was the only serum inflammatory marker with significantly higher levels in the critical group than in the non-critical group. The fecal calprotectin level in the critical group was significantly higher than that in the non-critical group (P = 0.03), regardless of the presence of gastrointestinal symptoms. Stool metabolomic analysis showed that the level of indole-3-propionic acid, a ligand for aryl hydrocarbon receptor (AhR), was markedly decreased in the critical group compared to that in the non-critical group (P = 0.01). The expression of genes involved in tryptophan metabolism, including ACE2, AHR, CARD9, and IL22, was downregulated in the ileum of critical COVID-19 patients who required a colonoscopy. Discussion: Critical COVID-19 patients have gastrointestinal inflammation potentially caused by impaired tryptophan metabolism in the small intestine due to decreased expression of genes involved in tryptophan metabolism.

Elevated NETs and Calprotectin Levels after ChAdOx1 nCoV-19 Vaccination Correlate with the Severity of Side Effects.

ChAdOx1 nCoV-19 vaccination has been associated with the rare side effect; vaccine-induced immune thrombotic thrombocytopenia (VITT). The mechanism of thrombosis in VITT is associated with high levels of neutrophil extracellular traps (NETs). The present study examines whether key markers for NETosis, such as H3-NETs and calprotectin, as well as syndecan-1 for endotheliopathy, can be used as prognostic factors to predict the severity of complications associated with ChAdOx1 vaccination. Five patients with VITT, 10 with prolonged symptoms and cutaneous hemorrhages but without VITT, and 15 with only brief and mild symptoms after the vaccination were examined. Levels of H3-NETs and calprotectin in the vaccinated individuals were markedly increased in VITT patients compared to vaccinees with milder vaccination-associated symptoms, and a strong correlation (r ≥ 0.745, p < 0.001) was found with severity of vaccination side effects. Syndecan-1 levels were also positively correlated (r = 0.590, p < 0.001) in vaccinees to side effects after ChAdOx1 nCoV-19 vaccination. We hypothesize that the inflammatory markers NETs and calprotectin may be used as confirmatory tests in diagnosing VITT.

Role of fecal calprotectin as a hypoxic intestinal damage biomarker in COVID-19 patients.

BACKGROUND: Gastrointestinal manifestations of coronavirus disease 2019 (COVID-19) appear to be substantial. Fecal calprotectin is a promising biomarker in COVID-19 associated gastrointestinal inflammation; however, its role in the severity of COVID-19 remains limited. We conducted a study to analyze the relationship between the severity of COVID-19 and hypoxic intestinal damage. METHODS: We assessed the severity of 44 hospitalized COVID-19 pneumonia patients based on the PaO2/FiO2 (P/F) ratio. Inflammatory markers were measured from blood samples, and fecal calprotectin was obtained from stool samples. RESULTS: Median levels of fecal calprotectin in COVID-19 patients involved in this study (n = 44) were found to be markedly elevated along with the severity of hypoxemia, as seen in the non-acute respiratory distress syndrome (ARDS) group 21.4 µg/g (5.2-120.9), mild ARDS 54.30 µg/g (5.2-1393.7), moderate ARDS 169.6 µg/g (43.4-640.5), and severe ARDS 451.6 µg/g (364.5-538.6). We also found significant differences in fecal calprotectin levels based on the severity of ARDS (P < 0.001), and although the patients were divided into ARDS and non-ARDS groups (P < 0.001). Furthermore, we found a strong negative correlation between the P/F ratio and fecal calprotectin levels (r = - 0.697, P < 0.001). CONCLUSION: Our findings support the potential role of fecal calprotectin as a biomarker of intestinal inflammation in COVID-19 as a consequence of hypoxic intestinal damage and as suggested by the reduced P/F ratio.

Clinical utility of circulating calprotectin to assist prediction and monitoring of COVID-19 severity: An Italian study.

BACKGROUND: Calprotectin (S100A8/A9) has been identified as a biomarker that can aid in predicting the severity of disease in COVID-19 patients. This study aims to evaluate the correlation between levels of circulating calprotectin (cCP) and the severity of COVID-19. METHODS: Sera from 245 COVID-19 patients and 110 apparently healthy individuals were tested for calprotectin levels using a chemiluminescent immunoassay (Inova Diagnostics). Intensive care unit (ICU) admission and type of respiratory support administered were used as indicators of disease severity, and their correlation with calprotectin levels was assessed. RESULTS: Samples from patients in the ICU had a median calprotectin concentration of 11.6 µg/ml as compared to 3.5 µg/ml from COVID-19 patients who were not in the ICU. The median calprotectin concentration in a cohort of healthy individuals collected before the COVID-19 pandemic was 3.0 µg/ml (95% CI: 2.820-2.969 µg/ml). Patients requiring a Venturi mask, continuous positive airway pressure, or orotracheal intubation all had significantly higher values of calprotectin than controls, with the increase of cCP levels proportional to the increasing need of respiratory support. CONCLUSION: Calprotectin levels in serum correlate well with disease severity and represent a promising serological biomarker for the risk assessment of COVID-19 patients.