Cave diving is a complex underwater activity associating multiple physiological, environmental stressors including high pressure, physical exertion, hyperoxia, cold and confined environment. We investigated the evolution of the oxidative–inflammatory stress, appetite hormones response, neurotransmitter and hydration status on a cohort of cave divers during repetitive dives (three days). Eleven male scuba-divers were divided into two groups in two Slovenian Caves. Based on the cave depth, they were classified: “Shallow” and “Deep”. Urine and saliva were collected before (T0) and after (T1) each dive. Reactive oxygen species (ROS), total antioxidant capacity (TAC), lipid peroxidation (8-iso-PGF2α), inflammatory status (Interleukin-6), cortisol, leptin, ghrelin, dopamine, creatinine, neopterin, and electrolytes balance changes were investigated. A significant post-dive decrease in body temperature was observed in “Deep” dives, with values dropping from pre- to post-dive on 2nd and 3rd day, indicating marked thermal stress during cave diving. In both groups, significant changes in oxy-inflammation were found with bigger changes in “Deep” group compared to “Shallow”. Significant hormonal changes occurred only in the “Deep” group, with increased leptin and decreased ghrelin post-dive, while cortisol remained with higher concentrations in the “Shallow” group. Dopamine levels significantly increased post-dive in both groups, with a greater rise observed in the “Deep” group. Repetitive cave dives induced a progressive change in oxidative stress, inflammation biomarker, and some hormones.

BACKGROUND:Detection of monoclonal components (MCs) using serum and urine immunofixation (IFE) and free light chain measurement is a critical early step in diagnosing cardiac amyloidosis. Patients with MCs are referred for biopsy-based diagnostic work-up. New reference ranges for the free light chain ratio (FLCR), adjusted for age and estimated glomerular filtration rate, have been proposed. OBJECTIVES:The aim of this study was to compare the diagnostic performance of the new vs the conventional FLCR in patients with light chain (AL) amyloidosis and wild-type transthyretin (ATTRwt) amyloidosis. METHODS:The analysis included 1,705 patients with AL amyloidosis and 675 with ATTRwt amyloidosis. RESULTS:In the AL cohort, 44 patients (3%) had negative results on serum and urine IFE at diagnosis. Among these, 13 patients had normal conventional FLCRs and 15 had normal new FLCRs, with no significant difference in diagnostic sensitivity (70.4% [95% CI: 55.8%-82.5%] vs 65.9% [95% CI: 50.0%-79.5%]; P = 0.82). Overall diagnostic sensitivity for MC detection was similar between the new and conventional FLCRs (99.2% vs 99.1%). Among patients with ATTRwt amyloidosis and negative serum and urine IFE results, 156 (26.5%) had abnormal FLCRs using the conventional cutoff, compared with only 12 (2%) using the new FLCR. At hematologic response assessment in AL amyloidosis, concordance in the definition of complete response between the 2 FLCR methods was 94.9% (95% CI: 93.4%-95.9%). CONCLUSIONS:The new FLCR demonstrates equivalent diagnostic sensitivity in AL amyloidosis and can be integrated into complete response criteria. In patients with suspected ATTRwt amyloidosis, it significantly reduces the proportion of FLCR-only abnormalities, thereby limiting the need for biopsy confirmation.

Background:SCUBA diving involves exposure to a hyperbaric environment that can induce oxidative stress and inflammation. This study investigates the evolution of oxy-inflammation status in divers who performed repetitive dives in cold water. Methods:In the Baltic Sea, nine expert divers were recruited to perform five dives (T1-T5). Urine and saliva were collected before (A) and after (B) each dive. Reactive Oxygen Species (ROS), total antioxidant capacity (TAC), lipid peroxidation (8-iso-PGF2α), DNA damage (8-OH-dG), inflammatory status (IL-6), nitric oxide metabolites, neopterin, and electrolyte balance changes were investigated. Results:Pre-dive values showed significant increases at the fourth to fifth days in ROS (+45 and +89%) and consequently in lipid peroxidation (+65%) at the fourth day and in DNA damage (+49 and +61%) at the fourth to fifth days, respectively, compared to the first day value. Post-dive significant increases were recorded at the fourth to fifth days in ROS (+83 % and +146%), and at the fifth day in lipid peroxidation (+59%) and DNA damage (+41%) with respect to the post-dive value of the first day. TAC showed a decrease from the fourth to fifth days post-dive (-15% and -24%) compared to the value on the first day post-dive. Finally, IL-6 increased at the basal level of the fifth day (+183%) and post dive (+154%) with respect to the corresponding values of the first day. Conclusion:Repetitive dives in cold water induced a progressive increase in pre-dive ROS, 8-iso-PGF2α, 8-OH-dG, and IL-6. Oxidative stress was only partially contained by activation of endogenous antioxidant defenses, while IL-6 variation resulted from diving-related physical effort or oxy-inflammation. We did not find notable changes in the electrolyte balance, probably because all subjects examined were well- trained and experienced divers.

Background/Objectives: Endurance exercise increases oxygen demand and, when not balanced by antioxidant defenses, consequently, oxidative stress and inflammatory cytokines increase too. In breast cancer survivors (BCS), post-treatment, physical capacity decreases, lowering life quality. Dragon boat (DB) paddling has shown benefits in reducing lymphedema and improving psychological well-being. This study aimed at non-invasively investigating in BCS, by means of saliva and urine samples, the systemic responses to oxy-inflammation, and appetite hormones after a DB endurance race. Methods: 15 BCS and 15 healthy women (5 (CTR) who performed the DB race too) were studied. BCS and CTR were monitored pre- and post-race. Reactive oxygen species (ROS) production, total antioxidant capacity (TAC), lipid peroxidation (8-iso), DNA oxidation (8-OH-dG), nitric oxide metabolites (NOx), inflammation markers (IL-6-10 and TNFα), appetite hormones, electrolytes concentration, psychometric, and physical scales were assessed. Results: At rest, compared to healthy women, BCS showed a significant increase in oxy-inflammation biomarkers. BCS showed a general increase in oxy-inflammation parameters compared to CTR after the DB race. In BCS, there were the following results: ROS: +80%; lipid peroxidation: +103%; DNA oxidation: +44%; interleukins-6: +179%; IL-10: +55%; TNFα: +9%, NOx: +60% increases and unbalanced appetite hormones: leptin (-32%); and ghrelin (+53%). Moreover, the dragon boat offered a holistic approach to recovery, addressing emotional and social needs supporting belonging, love, and esteem needs, reported to be about 56% of the motivations in this activity, while post-race the following increased: a sense of fatigue (+55%); tiredness (48%); a cold sensation (+15%); and +32% pain. Conclusions: This study provided evidence that, in BCS, a DB endurance race produces an important imbalance in the oxy-inflammation state, at the same time being accompanied by a positive impact on subjective mood and general wellness. Future studies should focus on long-term effects.

SCUBA diving poses risks due to pressure changes during descent (compression) and ascent (decompression). Decompression sickness (DCS) occurs due to gas bubble formation as the pressure decreases, causing joint pain, numbness, dizziness, or even paralysis and death. Immediate treatment involves 100% oxygen to help eliminate inert gases and hyperbaric oxygen therapy (HBOT), which is essential to reduce gas emboli formation and inflammation, thus improving symptoms. We evaluated oxy-inflammation biomarkers in the saliva and urine of nine subjects pre- and post-technical dive on the Haven wreck (GE, Italy). A case of DCS occurred during the dive. The injured diver was treated immediately with O2 and transported to the hyperbaric center of “ASST Ospedale Ca Granda” in Milan. He was treated following the U.S. Navy Treatment Table 5 at 2.8 ATA and the day after with Table 15 at 2.4 ATA. Venous blood and urine samples were collected before and after each HBO treatment. Our study shows that dive increased oxy-inflammation biomarkers (ROS +126%; lipid peroxidation +23%; interleukins-6 +81%, -1β +19%, and TNFα +84%) and nitric oxide metabolites levels (+36%). HBOT after a DCS episode reduced oxidative stress, lowering the very high marker of lipid peroxidation (8-iso-PGF2α), and inhibited inflammatory interleukins. Overall, HBOT improved physiological responses in the diver affected by DCS.

Freeskiing is performed in an extreme environment, with significant physical effort that can induce reactive oxygen species (ROS) generation and dehydration. This study aimed to investigate the evolution of the oxy-inflammation and hydration status during a freeskiing training season with non-invasive methods. Eight trained freeskiers were investigated during a season training: T0 (beginning), T1-T3 (training sessions), and T4 (after the end). Urine and saliva were collected at T0, before (A) and after (B) T1-T3, and at T4. ROS, total antioxidant capacity (TAC), interleukin-6 (IL-6), nitric oxide (NO) derivatives, neopterin, and electrolyte balance changes were investigated. We found significant increases in ROS generation (T1A-B +71%; T2A-B +65%; T3A-B +49%; p < 0.05–0.01) and IL-6 (T2A-B +112%; T3A-B +133%; p < 0.01). We did not observe significant variation of TAC and NOx after training sessions. Furthermore, ROS and IL-6 showed statistically significant differences between T0 and T4 (ROS +48%, IL-6 +86%; p < 0.05). Freeskiing induced an increase in ROS production, which can be contained by antioxidant defense activation, and in IL-6, as a consequence of physical activity and skeletal muscular contraction. We did not find deep changes in electrolytes balance, likely because all freeskiers were well-trained and very experienced.

BACKGROUND:Vitamin D (VitD) deficiency has been reported to be associated with respiratory tract infection. In this work we evaluated the concentration of VitD in COVID-19 patients experiencing acute respiratory infections of different levels of severity excluding those who underwent invasive respiratory support. METHODS:The levels of serum VitD and C-reactive protein (CRP) were analyzed in 118 consecutive hospitalized COVID-19 patients (74 male, 44 female), confirmed with rRT-PCR. Of these patients with ventilation support 52 (44.1%) received oxygen via nasal cannula, oxygen mask or an oxygen mask with a reservoir, 48 (40.7%) were on a continuous positive airway pressure device (CPAP) and 18 (15,3%) on non-invasive mechanical ventilation (NIMV). RESULTS:The median values (range) of VitD and of CRP were 15.1 ng/mL (1.3-73.3) and 14.2 mg/L (5.0-151.2), respectively. A negative correlation from VitD levels and those of CRP (correlation coefficient: 0.259: P=0.005) was observed. VitD levels in O2 support patients were significantly higher than in both CPAP and NIMV patients. No statistical differences were found for CRP levels (P=0.834) among the three type of oxygen support. Fewer patients with O2 support had VitD <30 ng/mL and <20 ng/mL than CPAP and NIMV patients. There were no relationships between VitD and the three classes of IgM (P=0.419) and of IgG (P=0.862) SARS-CoV-2 antibodies values. The behavior was the same for CRP. CONCLUSIONS:Our study shows that a significant proportion of COVID-19 patients have a VitD deficiency and that this condition is more frequent in CPAP and in NIMV patients.

(1) Background: SCUBA diving can influence changes of several hematological parameters (HP) but the changes of HP in the decompression phases are still unclear. The aim of this study was to investigate any possible relationship between HP and predisposition to inert gas bubble formation after a single recreational dive. (2) Methods: Blood, obtained from 32 expert SCUBA divers, was tested for differences in white blood cells (WBC), granulocytes (GRAN), lymphocytes (LYM), and monocytes (MONO), red blood cells (RBC), and platelets (PLT) between bubblers (B) and non-bubblers (NB). (3) Results: We found inter-subject differences in bubble formation (considering the same diving profile performed by the divers) and a statistically significant higher number of total WBC, GRAN and LYM in NB as compared to the B divers in the pre and in the post diving sample, while no statistical differences were found for MONO and PLT. In addition, we did not find any statistically significant difference between NB and B in RBC. (4) Conclusions: Our results, even if in absence of investigated anti-inflammatory markers, could indicate a relationship between low WBC numbers and bubble formation. This aspect may explain a possible cause of inter-subject differences in bubble formation in divers performing the same dive profile.

Background The aim of this work was to investigate the serum amino acid (AA) changes after a breath-hold diving (BH-diving) training session under several aspects including energy need, fatigue tolerance, nitric oxide (NO) production, antioxidant synthesis and hypoxia adaptation. Twelve trained BH-divers were investigated during an open sea training session and sampled for blood 30 min before the training session, 30 min and 4 h after the training session. Serum samples were assayed for AA changes related to energy request (alanine, histidine, isoleucine, leucine, lysine, methionine, proline threonine, valine), fatigue tolerance (ornithine, phenylalanine, tyrosine), nitric oxide production (citrulline), antioxidant synthesis (cystine, glutamate, glycine) and hypoxia adaptation (serine, taurine). Main results Concerning the AA used as an energy support during physical effort, we found statistically significant decreases for all the investigated AA at T1 and a gradual return to the basal value at T2 even if alanine, proline and theonine still showed a slight significant reduction at this time. Also, the changes related to the AA involved in tolerance to physical effort showed a statistically significant decrease only at T1 respect to pre-diving value and a returned to normal value at T2. Citrulline, involved in NO production, showed a clear significant reduction both at T1 and T2. Concerning AA involved in endogenous antioxidant synthesis, the behaviour of the three AA investigated is different: we found a statistically significant increase in cystine both at T1 and T2, while glycine showed a statistically significant reduction (T1 and T2). Glutamate did not show any statistical difference. Finally, we found a statistically significant decrease in the AA investigated in other hypoxia conditions serine and taurine (T1 and T2). Conclusions Our data seem to indicate that the energetic metabolic request is in large part supported by AA used as substrate for fuel metabolism and that also fatigue tolerance, NO production and antioxidant synthesis are supported by AA. Finally, there are interesting data related to the hypoxia stimulus that indirectly may confirm that the muscle apparatus works under strong exposure conditions notwithstanding the very short/low intensity of exercise, due to the intermittent hypoxia caused by repetitive diving.

Chronic kidney disease (CKD) patients are more susceptible to infections compared to the general population. SARS-CoV-2 virus pathology is characterized by a cytokine storm responsible for the systemic inflammation typical of the COVID-19 disease. Since CKD patients have a reduced renal clearance, we decided to investigate whether they accumulate harmful mediators during the COVID-19 disease. We conducted a retrospective study on 77 COVID-19 hospitalized subjects in the acute phase of the illness. Thirteen different cytokines were assessed in plasma collected upon hospitalization. The patients were divided into three groups according to their estimated glomerular filtration rate, eGFR < 30 (n = 23), 30 < eGFR < 60 (n = 33), eGFR > 60 mL/min (n = 21). We found that Tumor Necrosis Factor α and its receptors I and II, Interleukin-7, Leukemia Inhibitory Factor, FAS receptor, Chitinase 3-like I, and the Vascular Endothelial Growth Factor showed an increased accumulation that negatively correlate with eGFR. Moreover, non-survivor patients with an impaired kidney function have significantly more elevated levels of the same mediators. In conclusion, there is a tendency in COVID-19 ESRD patients to accumulate harmful cytokines. The accumulation seems to associate with mortality outcomes and may be due to reduced clearance but also to increased biosynthesis in most severe cases.

Patients with CKD on RRT are at high risk for severe disease and mortality in COVID-19 disease. We decided to conduct an observational prospective study to evaluate antibody response after vaccination for COVID-19 in a cohort of 210 adult patients on RRT (148 on HD; 20 on PD; and 42 kidney transplant recipients). Blood samples were taken before and 4 weeks after vaccination. Antibody levels were evaluated with CLIA immunoassay testing for IgG anti-trimeric spike protein of SARS-CoV-2. A positive antibody titer was present in 89.9% of HD patients, 90% of PD patients, and 52.4% of kidney transplant recipients. Non-responders were more frequent among patients on immunosuppressive therapy. Mycophenolate use in kidney transplant patients was associated with lower antibody response. The median antibody titer was 626 (228–1480) BAU/mL; higher in younger patients and those previously exposed to the virus and lower in HD patients with neoplasms and/or on immunosuppressive therapy. Only two patients developed COVID-19 in the observation period: they both had mild disease and antibody titers lower than 1000 BAU/mL. Our data show a valid response to COVID-19 mRNA vaccination in HD and PD patients and a reduced response in kidney transplant recipients. Mycophenolate was the most relevant factor associated with low response.

Introduction: In chronic kidney disease (CKD), the high morbidity and mortality risk for cardiovascular disease (CVD) are not easily explained only on the basis of traditional factors. Among nontraditional ones involved in CKD, malnutrition, inflammation, and atherosclerosis/calcification have been described as the “MIA syndrome.” Methods: In this pilot study, we evaluated the association between the variation in serum levels of 27 uremic retention solutes plus 6 indexes related to the MIA syndrome processes in a population of dialysis patients. Results: As expected, we found a direct correlation between serum albumin and both phosphate and total cholesterol (r = 0.54 and 0.37, respectively; p < 0.05). Moreover, total cholesterol and phosphate directly correlate (r = 0.40, p < 0.05). The relationship between malnutrition and inflammation is highlighted by the correlation of serum cholesterol levels with serum alpha-1 acid glycoprotein and IL-6 levels (r = −0.56, r = −0.39, respectively; p < 0.05). Moreover, the relation between inflammation and atherosclerosis/calcification is supported by the correlation of IL-6 with VEGF levels and vascular smooth muscle cell high-Pi in vitro calcification (r = 0.81, r = 0.66, respectively; p < 0.01). Conclusion: We found significant correlations between several uremic retention solutes and malnutrition, inflammation, and atherosclerosis/calcification. Our findings support the hypothesis of a central role of the uremic milieu in the MIA syndrome and ultimately in the pathogenesis of CKD-specific CVD risk factors.

Background: We explored the long-term effects of cART on markers of gut damage, microbial translocation, and paired gut/blood microbiota composition, with a focus on the role exerted by different drug classes. Methods: We enrolled 41 cART naïve HIV-infected subjects, undergoing blood and fecal sampling prior to cART (T0) and after 12 (T12) and 24 (T24) months of therapy. Fifteen HIV-uninfected individuals were enrolled as controls. We analyzed: (i) T-cell homeostasis (flow cytometry); (ii) microbial translocation (sCD14, EndoCab, 16S rDNA); (iii) intestinal permeability and damage markers (LAC/MAN, I-FABP, fecal calprotectin); (iv) plasma and fecal microbiota composition (alpha- and beta-diversity, relative abundance); (v) functional metagenome predictions (PICRUSt). Results: Twelve and twenty four-month successful cART resulted in a rise in EndoCAb (p = 0.0001) and I-FABP (p = 0.039) vis-à-vis stable 16S rDNA, sCD14, calprotectin and LAC/MAN, along with reduced immune activation in the periphery. Furthermore, cART did not lead to substantial modifications of microbial composition in both plasma and feces and metabolic metagenome predictions. The stratification according to cART regimens revealed a feeble effect on microbiota composition in patients on NNRTI-based or INSTI-based regimens, but not PI-based regimens. Conclusions: We hereby show that 24 months of viro-immunological effective cART, while containing peripheral hyperactivation, exerts only minor effects on the gastrointestinal tract. Persistent alteration of plasma markers indicative of gut structural and functional impairment seemingly parallels enduring fecal dysbiosis, irrespective of drug classes, with no effect on metabolic metagenome predictions.

BACKGROUNDVitamin D (VitD) deficiency has been reported to be associated with respiratory tract infection. In this work we evaluated the concentration of VitD in COVID-19 patients experiencing acute respiratory infections of different levels of severity excluding those who underwent invasive respiratory support.METHODSThe levels of serum VitD and C-reactive protein (CRP) were analyzed in 118 consecutive hospitalized COVID-19 patients (74M, 44F), confirmed with rRT-PCR. Of these patients with ventilation support 52 (44.1%) received oxygen via nasal cannula, oxygen mask or an oxygen mask with a reservoir, 48 (40.7%) were on a continuous positive airway pressure device (CPAP) and 18 (15,3%) on non-invasive mechanical ventilation (NIMV).RESULTSThe median values (range) of VitD and of CRP were 15.1 ng/mL (1.3-73.3) and 14.2 mg/L (5.0-151.2), respectively. A negative correlation from VitD levels and those of CRP (correlation coefficient - 0.259: P=0.005) was observed. VitD levels in O2 support patients were significantly higher than in both CPAP and NIMV patients. No statistical differences were found for CRP levels (P=0.834) among the three type of oxygen support. Fewer patients with O2 support had VitD <30 ng/mL and <20 ng/mL than CPAP and NIMV patients. There were no relationships between VitD and the three classes of IgM (P=0.419) and of IgG (P=0.862) SARS-CoV-2 antibodies values. The behavior was the same for CRP.CONCLUSIONSOur study shows that a significant proportion of COVID-19 patients have a VitD deficiency and that this condition is more frequent in CPAP and in NIMV patients.

Cytosine arabinoside (ara-C) is rapidly deaminated in vivo to ara-U by cytidine-deoxycytidine deaminase. The purpose of this study was to determine the contribution of the deamination pathway to the overall clearance of ara-C after a single dose to rabbits, as well as to determine the pharmacokinetics of ara-U itself. Male rabbits were cannulated in the marginal ear vein and received a single IV bolus dose (50 mg kg-1) of either ara-C (n = 10) or ara-U (n = 10). Blood samples were collected for up to 24 h. One week later, the rabbits received the opposite treatment. Plasma samples were analyzed by reversed-phase HPLC. The plasma clearance of ara-C (8.16 +/- 2.43 ml min-1 kg-1) was significantly higher than the clearance of ara-U (5.66 +/- 2.59 ml min-1 kg-1). The volume of distribution of ara-C was 0.64 +/- 0.16 l kg-1 (mean +/- SD) and was significantly smaller (p less than 0.05) than that of ara-U (1.22 +/- 0.70 l kg-1). As a result, the elimination rate constant of ara-C was significantly larger than that of ara-U (0.602 +/- 0.097 h-1 vs 0.258 +/- 0.05 l h-1). In the rabbits that received both treatments (n = 7), the fraction of the ara-C dose metabolized to ara-U (fm) was 0.53 +/- 0.20. Qualitatively, the pharmacokinetics of ara-C and ara-U resemble those in humans. This study provides the basis for further work into the modulation of ara-C disposition either by ara-U or other agents.

Background Breath-hold diving (BH-diving) is associated to extreme environmental conditions, prolonged physical activity, and complex adaptation mechanisms to supply enough O 2 to vital organs. Consequently, one of the biggest effects could be an increased exercise-induced muscle fatigue, in both skeletal and cardiac muscles that can induce an increase of muscles injury markers including creatine kinase (CK), aspartate transferase (AST), and alanine transferase (ALT) when concerning the skeletal muscle, cardiac creatine kinase isoenzyme (CK-MBm) and cardiac troponin I (cTnI) when concerning the cardiac muscle, and lactate dehydrogenase (LDH) as index of muscle stress. The aim of this study is to investigate serum cardiac and skeletal muscle markers before and after a BH-diving training session. Results We found statistically significant increases of CK (T0: 136.1% p < 0.0001; T1: 138.5%, p < 0.0001), CK-MBm (T0: 145.1%, p < 0.0001; T1: 153.2%, p < 0.0001) LDH (T0: 110.4%, p < 0.0003; T1: 110.1%, p < 0.0013) in both T0 and T1 blood samples, as compared to basal value. AST showed a statistically significant increase only at T0 (106.8%, p < 0.0007) while ALT did not exhibit statistically significant changes. We did not find any changes in cTnI levels between pre-dive and post-dive samples. Conclusions Our data seem to indicate that during a BH-diving training session, skeletal and cardiac muscles react to physical effort releasing stress-related substances. Although the peculiar nature of BH-diving makes it difficult to understand if our results are related only to exercise induced muscle adaptation or whether acute hypoxia or a response to environmental changes (pressure) play a role to explain the observed changes, further studies are needed to better understand if these biomarker changes are linked to physical exercise or to acute hypoxia, or if both conditions play a role.

Glyphosate is a non-selective systemic herbicide used in agriculture. For almost half a century, the International Agency for Research on Cancer has run a Monographs program, the conclusion in March 2015 that glyphosate is “probably carcinogenic to humans” in addition to being genotoxic and carcinogenic in animals, while the regulatory European Food Safety Authority have asserted that glyphosate poses no public risk. The scientific debate is still lively. We collected detailed socio-demographic, occupational exposures and health surveillance information for 26 winegrowers as aim to investigate exposure to glyphosate and other pesticide. Exposure was assessed through biological monitoring (24-hour urine collection), immune function (IL-4, IL-5, IL-8, IL-12, IL- 17, IL-33, IFN- γ), transcriptional and post transcriptional alterations (miRNA) and genotoxic effects (Comet assay). The exposure conditions in our winegrowers, as referred to the parameters so far analyzed, did not reveal a significant glyphosate absorption nor significant health concerns.

Background: Gastrointestinal manifestations of COVID-19 have been well established, but pancreatic involvement is under debate To evaluate the presence of acute pancreatitis in COVID-19 patient in a prospective, unicenter cohort study Methods: From April 1, 2020 to April 30, 2020, 110 consecutive patients (69 males, 41 females;mean age 63 0 years [range, 24-93 years]) met these criteria and were enrolled in the study The clinical data and serum activity of pancreatic amylase and lipase were assayed in all patients using commercially available kits Results: The average time from the onset of respiratory symptoms to the blood samples was 22 2 days (range, 0-47) None of the patients studied developed clinical signs ormorphological alterations compatiblewith acute pancreatitis according to the Atlanta revised criteria It was found that 24 5% of the patients had amylase values above 53 IU/L and 16 4% had lipase values above 300 IU/L Only one patient (0 9%) had both amylase and lipase values in excess of three-fold the upper normal limit without clinical signs of pancreatitis There were no statistically significant difference in amylase and lipase serum activities in patients having nausea/vomiting (amylase: 32 1 ± 18 7 IU/L, P = 0 438;lipase: 80 7 ± 42 4 IU/L, P = 0 134) and in those who did not (amylase: 46 3 ± 35 7 IU/L;lipase: 200 3 ± 240 0 IU/L), or in patients having diarrhea (amylase: 65 4 ± 64 2 IU/L, P = 0 198;lipase: 303 0 ± 544 4 IU/L, P = 0 615) and in those who did not (amylase: 43 1 ± 28 5 IU/L;lipase: 181 5 ± 149 3 IU/L) Regarding the oxygen support, a statistical difference was found in amylase serum activities among the various types of oxygen support used (amylase P = 0 047) whereas this difference was not found for lipase (P = 0 065) Conclusions: The presence of pancreatic hyperenzymemia in a patient with COVID-19 requires the management of these patients be guided by clinical evaluation and not merely by evaluation of the biochemical results

Background: Since December 2019, COVID-19 has widely spread throughout the world, causing thousands of deaths. Clinical characteristics of COVID-19 patients have been widely reported, but significative disease-associated biomarkers are needed. We aimed to evaluate the prognostic power of circulating sphingosine-1-phosphate (S1P) in COVID-19, to propose S1P as a novel prognostic and predictive biomarker. Methods: Clinical and blood parameters were investigated in 111 COVID-19 patients (COV) and 47 healthy subject (HLT), with a particular focus on patients who required intensive care unit (ICU) admission. We measured serum levels of S1P and its main transporter apolipoprotein M (apoM) by ELISA assay. Correlation with clinical and blood parameters were performed by Pearson correlations. Univariable and multivariable regression analysis were performed to assess the interaction between clinically significant factors and ICU admission. Further, Cox regression was used to evaluate the prognostic power of S1P for ICU admission and mortality.Findings: We reported statistically significant alterations of several blood parameters in COV, as an increase of white blood cells, neutrophil-to-lymphocyte ratio, ferritin, D-dimer and fibrinogen, and a decrease in hemoglobin, lymphocyte count and total proteins. Our major finding is the drop of serum S1P level in COV, strongly associated with the decrease of red blood cells, the major source of plasmatic S1P, and both apoM and albumin, the most important transporters of circulating S1P. The multivariable regression analysis revealed that S1P is the most important predictor for ICU admission (OR:39·45, [95%CI:1·51-1031·60]; p=0·027), and Cox proportional-hazards model demonstrated a high power of S1P in predicting patient's outcome.Interpretation: COVID-19 patients showed a drastic decrease of serum S1P, suggesting that circulating S1P levels may be clinically used as negative biomarkers to predict severity/mortality of COVID-19. Taken together, our results suggest that restoring S1P at physiological level may represent a novel therapeutic strategy.Funding: Italian Ministry of Health.Declaration of Interests: All authors declare no competing interests.Ethics Approval Statement:This prospective, case-control study was approved by the Ethic Committee of Ospedale San Paolo in Milan, Lombardy, Italy (COST Action n.2020/ST/057).

Background COVID-19 is an infectious disease caused by a novel coronavirus (SARS-CoV-2). The immunopathogenesis of the infection is currently unknown. Healthcare workers (HCWs) are at highest risk of infection and disease. Aim of the study was to assess the sero-prevalence of SARS-CoV-2 in an Italian cohort of HCWs exposed to COVID-19 patients. Methods A point-of-care lateral flow immunoassay (BioMedomics IgM-IgG Combined Antibody Rapid Test) was adopted to assess the prevalence of IgG and IgM against SARS-CoV-2. It was ethically approved (“Milano Area 1” Ethical Committee prot. n. 2020/ST/057). Results A total of 202 individuals (median age 45 years; 34.7% males) were retrospectively recruited in an Italian hospital (Milan, Italy). The percentage (95% CI) of recruited individuals with IgM and IgG were 14.4% (9.6–19.2%) and 7.4% (3.8–11.0%), respectively. IgM were more frequently found in males (24.3%), and in individuals aged 20–29 (25.9%) and 60–69 (30.4%) years. No relationship was found between exposure to COVID-19 patients and IgM and IgG positivity. Conclusions The present study did show a low prevalence of SARS-CoV-2 IgM in Italian HCWs. New studies are needed to assess the prevalence of SARS-CoV-2 antibodies in HCWs exposed to COVID-19 patients, as well the role of neutralizing antibodies.