Candida lipolytica Bloodstream Infection in an Adult Patient with COVID-19 and Alcohol Use Disorder: A Unique Case and a Systematic Review of the Literature.

Candida lipolytica is an uncommon Candida species causing invasive fungemia. This yeast is mainly associated with the colonisation of intravascular catheters, complicated intra-abdominal infections, and infections in the paediatric population. Here, we report a case of C. lipolytica bloodstream infection in a 53-year-old man. He was admitted for an alcohol withdrawal syndrome and mild COVID-19. Among the primary risk factors for candidemia, only the use of broad-spectrum antimicrobials was reported. The empiric treatment was commenced with caspofungin and then targeted with intravenous fluconazole. Infective endocarditis was ruled out using echocardiography, and PET/TC was negative for other deep-seated foci of fungal infection. The patient was discharged after blood culture clearance and clinical healing. To the best of our knowledge, this is the first case of C. lipolytica candidemia in a patient with COVID-19 and alcohol use disorder. We performed a systematic review of bloodstream infections caused by C. lipolytica. Clinicians should be aware of the possibility of C. lipolytica bloodstream infections in patients with alcohol use disorder, especially in a COVID-19 setting.

The Impact of Serum Albumin Levels on COVID-19 Mortality.

Low serum albumin (SA) correlates with mortality in critically ill patients, including those with COVID-19. We aimed to identify SA thresholds to predict the risk of longer hospital stay, severe respiratory failure, and death in hospitalized adult patients with COVID-19 pneumonia. A prospective longitudinal study was conducted at the Infectious Diseases Unit of Trieste University Hospital (Italy) between March 2020 and June 2021. The evaluated outcomes were: (1) need of invasive mechanical ventilation (IMV); (2) length of hospital stay (LOS); and (3) 90-day mortality rate. We enrolled 864 patients. Hypoalbuminemia (<3.5 g/dL) was detected in 586 patients (67.8%). SA on admission was significantly lower in patients who underwent IMV (2.9 vs. 3.4 g/dL; p < 0.001). The optimal SA cutoff predicting the need of IMV was 3.17 g/dL (AUC 0.688; 95% CI: 0.618-0.759; p < 0.001) and this threshold appeared as an independent risk factor for the risk of IMV in multivariate Cox regression analysis. The median LOS was 12 days and a higher SA was predictive for a shorter LOS (p < 0.001). The overall 90-day mortality rate was 15%. SA was significantly lower in patients who died within 90 days from hospital admission (3.1 g/dL; IQR 2.8-3.4; p < 0.001) as compared to those who survived (3.4 g/dL; IQR 3.1-3.7). The optimal SA threshold predicting high risk of 90-day mortality was 3.23 g/dL (AUC 0.678; 95% CI: 0.629-0.734; p < 0.001). In a multivariate Cox regression analysis, SA of <3.23 g/dL appeared to be an independent risk factor for 90-day mortality. Our results suggest that low SA on admission may identify patients with COVID-19 pneumonia at higher risk of severe respiratory failure, death, and longer LOS. Clinicians could consider 3.2 g/dL as a prognostic threshold for both IMV and mortality in hospitalized COVID-19 patients.

A combined role for low vitamin D and low albumin circulating levels as strong predictors of worse outcome in COVID-19 patients.

PURPOSE: We aimed to assess the combined role of vitamin D and albumin serum levels as predictors of COVID-19 disease progression. METHODS: We conducted a prospective observational study on adult patients hospitalized for SARS-CoV-2 pneumonia (March-September 2020). Vitamin D and albumin serum levels were measured on admission. These variables were categorized in albumin < 3.5 or ≥ 3.5 g/dL and vitamin D < 30 ng/mL or ≥ 30 ng/mL. We excluded patients with known bone diseases, renal failure, hypercalcemia and/or treated with antiepileptic drugs and steroids, and patients who received previous vitamin D supplementation. A composite outcome including any ventilatory support, PaO2/FiO2 ratio, and 60-day mortality was defined. RESULTS: Sixty-nine patients were enrolled, of whom 50% received non-invasive (NIV) or invasive mechanical ventilation (IMV), 10% died, whereas 89% and 66% presented low albumin and low vitamin D serum levels, respectively. No correlation between vitamin D and albumin levels was found. In multivariable logistic regression analyses adjusted for sex and age-corrected comorbidities, patients having albumin < 3.5 g/dL and vitamin D < 30 ng/mL showed a significant increased risk for all study outcomes, namely NIV/IMV (OR 3.815; 95% CI 1.122-12.966; p = 0.032), NIV/IMV or death (OR 3.173; 95% CI 1.002-10.043; p = 0.049) and PaO2/FIO2 ≤ 100 (OR 3.410; 95% CI 1.138-10.219; p = 0.029). CONCLUSION: The measurement of both vitamin D and serum albumin levels on COVID-19 patients' admission, and their combined evaluation, provides a simple prognostic tool that could be employed to guide prompt clinical decisions.

Potential of outpatient steroid therapy in elderly patients with early COVID-19.

Corticosteroids lower mortality in hospitalized patients with COVID-19 pneumonia requiring oxygen support. In this observational retrospective study (September 2020-June 2021), we explored the association between receiving home corticosteroids without oxygen supply and 30-day mortality in hospitalized patients with COVID-19 pneumonia. Among a total of 794 COVID-19 pneumonia patients, 763 were included into the study (males 68%; mean age 65 ±12 years), of whom 197 (26%) received home corticosteroids (mean daily prednisone equivalent-dose 40 mg ± 12 mg; range 10-50 mg; median 50 mg; IQR 25-50 mg; for 4 days). The overall 30-day mortality of the study population was 12%. The risk of death-adjusted for age, comorbidities, administration of remdesivir and respiratory failure severity-was lower (HR 0.405; p = 0.024) in patients receiving home corticosteroids. After stratifying the study population by age categories, home corticosteroids were associated with an adjusted decrease in mortality risk in patients > 77 years (HR 0.346; p = 0.040). Home corticosteroids may lower the 30-day mortality in elderly COVID-19 patients.

Discriminatory Value of Adiponectin to Leptin Ratio for COVID-19 Pneumonia.

Purpose: Obesity is a risk factor for severe coronavirus disease 2019 (COVID-19). Circulating adipokines have been associated with inflammatory burden and amplified or dysregulated immune responses. This study aimed to evaluate the discriminatory ability of adipokines to identify COVID-19 pneumonia and to assess disease severity. Methods: We conducted an observational case-control study, with a prospective design, and recruited patients with diagnosis of COVID-19 pneumonia (n = 48) and healthy controls (n = 36), who were matched by age, sex, and BMI. Leptin, adiponectin, IL-6, and TNF-α were measured by ELISA. Results: Patients with COVID-19 pneumonia had higher levels of leptin, lower adiponectin/leptin (Adpn/Lep) ratio, and higher expression of IL-6. Leptin had an acceptable discriminatory accuracy for COVID-19 pneumonia in patients with BMI >30 (AUC 0.74 [0.58, 0.90]) with a cutoff of 7852 pg/mL and it was associated with maximum respiratory support. By contrast, Adpn/Lep had an excellent discriminatory accuracy for COVID-19 pneumonia in patients with BMI <25 (AUC 0.9 [0.74, 1.06]) with a cutoff of 2.23. Conclusion: Our data indicate that high Adpn/Lep (>2.23) in lean patients is consistent with a state of good health, which decreases in case of inflammatory states, ranging from adipose tissue dysfunction with low-grade inflammation to COVID-19 pneumonia.

Aspirin and Infection: A Narrative Review.

Acetylsalicylic acid (ASA) is one of the most commonly used drugs in the world. It derives from the extract of white willow bark, whose therapeutic potential was known in Egypt since 1534 BC. ASA's pharmacological effects are historically considered secondary to its anti-inflammatory, platelet-inhibiting properties; however, human studies demonstrating a pro-inflammatory effect of ASA exist. It is likely that we are aware of only part of ASA's mechanisms of action; moreover, the clinical effect is largely dependent on dosages. During the past few decades, evidence of the anti-infective properties of ASA has emerged. We performed a review of such research in order to provide a comprehensive overview of ASA and viral, bacterial, fungal and parasitic infections, as well as ASA's antibiofilm properties.

Reactivation of Herpes Simplex Virus Type 1 (HSV-1) Detected on Bronchoalveolar Lavage Fluid (BALF) Samples in Critically Ill COVID-19 Patients Undergoing Invasive Mechanical Ventilation: Preliminary Results from Two Italian Centers.

Reactivation of herpes simplex virus type 1 (HSV-1) has been described in critically ill patients with coronavirus disease 2019 (COVID-19) pneumonia. In the present two-center retrospective experience, we primarily aimed to assess the cumulative risk of HSV-1 reactivation detected on bronchoalveolar fluid (BALF) samples in invasively ventilated COVID-19 patients with worsening respiratory function. The secondary objectives were the identification of predictors for HSV-1 reactivation and the assessment of its possible prognostic impact. Overall, 41 patients met the study inclusion criteria, and 12/41 patients developed HSV-1 reactivation (29%). No independent predictors of HSV-1 reactivation were identified in the present study. No association was found between HSV-1 reactivation and mortality. Eleven out of 12 patients with HSV-1 reactivation received antiviral therapy with intravenous acyclovir. In conclusion, HSV-1 reactivation is frequently detected in intubated patients with COVID-19. An antiviral treatment in COVID-19 patients with HSV-1 reactivation and worsening respiratory function might be considered.

Potential links between COVID-19-associated pulmonary aspergillosis and bronchiectasis as detected by high resolution computed tomography.

PURPOSE: The aim of this observational study was to highlight high resolution CT scan characteristics of COVID-19-associated pulmonary aspergillosis (CAPA) with a focus on the detection of de-novo appeared or evolved bronchiectasis. METHODS: From March 2020 to May 2021, we enrolled 350 consecutive mechanically ventilated ICU patients with COVID-19. Patients with CAPA and at least one chest CT scan performed within 15 days from the diagnosis were included. Two radiologists were asked to identify typical and atypical signs of COVID-19 pneumonia. Bronchiectasis locations were described and a modified Reiff score was calculated, as severity score. A total of 19 CAPA patients (median age 71.0, Interquartile range (IQR) 62.5-75.0; male 16, 84.2%) were included. RESULTS: According to the 2020 ECMM/ISHAM criteria, 18 patients had probable CAPA and one had proven CAPA. The median time between hospital admission and CT scan was 21 days (IQR 14.5-25.0). The incidence of bronchiectasis in the study population was 57.9% (n = 11). Tubular bronchiectasis was detected in 10 patients and were scored as follows: three patients had a score of 1, three patients had a score of score 2, one patient had a score of 5 and four patients had a score of 6. Eight patients had a previous CT scan (performed at hospital admission), among them: 5 patients developed de-novo bronchiectasis, while 2 patients demonstrated a volumetric increase of bronchiectasis. At the 6-months follow-up, the mortality rate for patients with CAPA was >60%. CONCLUSION: the radiologic detection of de-novo appearance or volumetric increase of bronchiectasis in COVID-19 should lead clinicians to search for fungal superinfections.

Neck Circumference Predicts Mortality in Hospitalized COVID-19 Patients.

We aimed to determine whether neck circumference predicts mortality among hospitalized COVID-19 patients with respiratory failure. We performed a prospective multicenter (Italy and Brasil) study carried out from March to December 2020 on 440 hospitalized COVID-19 patients with respiratory failure. Baseline neck circumference was measured. The study outcome was 30- and 60-days mortality. Female and male participants were classified as "large neck" when exceeding fourth-quartile. Patients had a median age of 65 years (IQR 54-76), 68% were male. One-quarter of patients presented with grade-1 or higher obesity. The median neck circumference was 40 cm (IQR 38-43): 38 cm (IQR 36-40) for female and 41 cm (IQR 39-44) for male subjects. "Large neck" patients had a significantly higher prevalence of hypertension (63 vs. 48%), diabetes (33 vs. 19%), obesity (26 vs. 14%), and elevated C-reactive protein (CRP) (98 vs. 88%). The cumulative mortality rate was 13.1% (n = 52) and 15.9% (n = 63) at 30 and 60 days, respectively. After adjusting for age, BMI, relevant comorbidities, and high C-reactive protein to albumin ratio, "large neck" patients showed a significantly increased risk of death at 30- (adjusted HR 2.50; 95% CI 1.18-5.29; p = 0.017) and 60-days (adjusted HR 2.26; 95% CI 1.14-4.46; p = 0.019). Neck circumference is easy to collect and provides additional prognostic information to BMI. Among hospitalized COVID-19 patients with respiratory failure, those with large neck phenotype had a more than double risk of death at 30 and 60 days.

Profiling of Oral Microbiota and Cytokines in COVID-19 Patients.

The presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been recently demonstrated in the sputum or saliva, suggesting how the shedding of viral RNA outlasts the end of symptoms. Recent data from transcriptome analysis show that the oral cavity mucosa harbors high levels of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2), highlighting its role as a double-edged sword for SARS-CoV-2 body entrance or interpersonal transmission. Here, we studied the oral microbiota structure and inflammatory profile of 26 naive severe coronavirus disease 2019 (COVID-19) patients and 15 controls by 16S rRNA V2 automated targeted sequencing and magnetic bead-based multiplex immunoassays, respectively. A significant diminution in species richness was observed in COVID-19 patients, along with a marked difference in beta-diversity. Species such as Prevotella salivae and Veillonella infantium were distinctive for COVID-19 patients, while Neisseria perflava and Rothia mucilaginosa were predominant in controls. Interestingly, these two groups of oral species oppositely clustered within the bacterial network, defining two distinct Species Interacting Groups (SIGs). COVID-19-related pro-inflammatory cytokines were found in both oral and serum samples, along with a specific bacterial consortium able to counteract them. We introduced a new parameter, named CytoCOV, able to predict COVID-19 susceptibility for an unknown subject at 71% of power with an Area Under Curve (AUC) equal to 0.995. This pilot study evidenced a distinctive oral microbiota composition in COVID-19 subjects, with a definite structural network in relation to secreted cytokines. Our results would be usable in clinics against COVID-19, using bacterial consortia as biomarkers or to reduce local inflammation.

High fecal calprotectin levels are associated with SARS-CoV-2 intestinal shedding in COVID-19 patients: A proof-of-concept study.

BACKGROUND: One third of coronavirus disease 2019 (COVID-19) patients have gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA has been detected in stool samples of approximately 50% of COVID-19 individuals. Fecal calprotectin is a marker of gastrointestinal inflammation in the general population. AIM: To investigate if fecal calprotectin correlates with SARS-CoV-2 intestinal shedding in COVID-19 patients with pneumonia. METHODS: Patients with SARS-CoV-2 pneumonia admitted to the Infectious Disease Unit (University Hospital of Trieste, Italy) from September to November 2020 were consecutively enrolled in the study. Fecal samples were collected and analyzed for quantification of fecal calprotectin (normal value < 50 mg/kg) and SARS-CoV-2 RNA presence by polymerase chain reaction (PCR). Inter-group differences were determined between patients with and without diarrhea and patients with and without detection of fecal SARS-CoV-2. RESULTS: We enrolled 51 adults (40 males) with SARS-CoV-2 pneumonia. Ten patients (20%) presented with diarrhea. Real-time-PCR of SARS-CoV-2 in stools was positive in 39 patients (76%), in all patients with diarrhea (100%) and in more than two thirds (29/41, 71%) of patients without diarrhea. Obesity was one of the most common comorbidities (13 patients, 25%); all obese patients (100%) (P = 0.021) tested positive for fecal SARS-CoV-2. Median fecal calprotectin levels were 60 mg/kg [interquartile range (IQR) 21; 108]; higher fecal calprotectin levels were found in the group with SARS-CoV-2 in stools (74 mg/kg, IQR 29; 132.5) compared to the group without SARS-CoV-2 (39 mg/kg, IQR 14; 71) (P < 0.001). CONCLUSION: High fecal calprotectin levels among COVID-19 patients correlate with SARS-CoV-2 detection in stools supporting the hypothesis that this virus can lead to bowel inflammation and potentially to the 'leaky gut' syndrome.

Spontaneous psoas haematoma: a life-threatening complication of anticoagulation in COVID-19. A case series of four episodes.

BACKGROUND: Anticoagulant prophylaxis is part of the standard management of hospitalized COVID-19 patients. Despite adequate thromboprophylaxis, one-third of COVID-19 patients with pneumonia developed pulmonary embolism. This high rate of thrombotic complications has led to higher doses of anticoagulants according to clinical complexity (e.g. intensive care unit (ICU) patients) and D-dimer levels. On the other side of the coin, haemorrhagic complications are being increasingly reported. CASES PRESENTATION: We herein report four cases of spontaneous psoas haematomas (SPH) among 548 patients hospitalized for SARS-CoV-2 pneumonia between March 2020 and January 2021 (incidence of 7.3 cases per 1000 patients). All patients had pneumonia, with age ranging between 62 and 83 years. All patients received anticoagulant therapy with low weight molecular heparin (100 U.I. anti-Xa/kg 2 times/d) from admission: in two cases, a diagnosis of pulmonary embolism was made. In another case, a thrombosis of left axillary and basilic veins was found, and only in one case anticoagulant therapy was started because of elevated levels of D-dimer. In all cases, signs of anaemia were detected and patients experienced low back or abdominal pain. The diagnosis of spontaneous psoas haematoma was made by computed tomography (CT) after a median of 12.5 d (9;16) from admission and 19.5 d (14.75; 24.25) from the beginning of COVID-19 symptoms. Half of these patients died from haemorrhagic shock. CONCLUSIONS: Given the potential life-threatening of SPH and the possible subtle clinical presentation, we believe it is crucial to raise clinicians awareness of this complication among COVID-19 patients undergoing anticoagulants.

Neck circumference as reliable predictor of mechanical ventilation support in adult inpatients with COVID-19: A multicentric prospective evaluation.

AIMS: COVID-19 is especially severe for elderly subjects with cardiometabolic and respiratory comorbidities. Neck circumference (NC) has been shown to be strongly related to cardiometabolic and respiratory illnesses even after adjustment for body mass index (BMI). We performed a prospective study to investigate the potential of NC to predict the need for invasive mechanical ventilation (IMV) in adult COVID-19 inpatients. MATERIALS AND METHODS: We prospectively and consecutively enrolled COVID-19 adult patients admitted to dedicated medical wards of two Italian hospitals from 25 March to 7 April 2020. On admission, clinical, biochemical and anthropometric data, including BMI and NC were collected. As primary outcome measure, the maximum respiratory support received was evaluated. Follow-up time was 30 days from hospital admission. RESULTS: We enrolled 132 subjects (55.0-75.8 years, 32% female). During the study period, 26 (19.7%) patients underwent IMV. In multivariable logistic regression analyses, after adjusting for age, sex, diabetes, hypertension and COPD, NC resulted independently and significantly associated with IMV risk (adjusted OR 1.260-per 1 cm increase 95% CI:1.120-1.417; P < .001), with a stronger association in the subgroup with BMI ≤30 Kg/m2 (adjusted OR 1.526; 95% CI:1.243-1.874; P < .001). NC showed a good discrimination power in predicting patients requiring IMV (AUC 0.783; 95% CI:0.684-0.882; P < .001). In particular, NC > 40.5 cm (>37.5 for females and >42.5 for males) showed a higher and earlier IMV risk compared to subjects with lower NC (Log-rank test: P < .001). CONCLUSIONS: NC is an easy to measure parameter able to predict the need for IMV in adult COVID-19 inpatients.

COVID-19-Induced Thrombosis in Patients without Gastrointestinal Symptoms and Elevated Fecal Calprotectin: Hypothesis Regarding Mechanism of Intestinal Damage Associated with COVID-19

Background: Patients with coronavirus infectious disease 2019 (COVID-19) and gastrointestinal symptoms showed increased values of fecal calprotectin (FC). Additionally, bowel abnormalities were a common finding during abdominal imaging of individuals with COVID-19 despite being asymptomatic. The current pilot study aims at evaluating FC concentrations in patients without gastrointestinal symptoms. Methods: we enrolled 25 consecutive inpatients with COVID-19 pneumonia, who were admitted without gastrointestinal symptoms and a previous history of inflammatory bowel disease. Results: At admission, 21 patients showed increased FC with median values of 116 (87.5;243.5) mg/kg despite absent gastrointestinal symptoms. We found a strong positive correlation between FC and D-Dimer (r = 0.745, p <0.0001). Two patients developed bowel perforation. Conclusion: our findings may change the current understanding of COVID-19 intestinal-related disease pathogenesis, shedding new light on the potential role of thrombosis and the consequent hypoxic intestinal damage.

The Model for Early COvid-19 Recognition (MECOR) Score: A Proof-of-Concept for a Simple and Low-Cost Tool to Recognize a Possible Viral Etiology in Community-Acquired Pneumonia Patients during COVID-19 Outbreak.

This study aims to assess the peripheral blood cell count "signature" of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) to discriminate promptly between COronaVIrus Disease 19 (COVID-19) and community-acquired pneumonia (CAP). We designed a retrospective case-control study, enrolling 525 patients (283 COVID-19 and 242 with CAP). All patients had a fever and at least one of the following signs: cough, chest pain, or dyspnea. We excluded patients treated with immunosuppressants, steroids, or affected by diseases known to modify blood cell count. COVID-19 patients showed a significant reduction in white blood cells (neutrophils, lymphocytes, monocytes, eosinophils) and platelets. We studied these parameters univariately, combined the significant ones in a multivariate model (AUROC 0.86, Nagelkerke PSEUDO-R2 0.5, Hosmer-Lemeshow p-value 0.9) and examined its discriminative performance in an internally-randomized validation cohort (AUROC 0.84). The cut-off selected according to Youden's Index (-0.13) showed a sensitivity of 84% and a specificity of 72% in the training cohort, and a sensitivity of 88% and a specificity of 73% in the validation cohort. In addition, we determined the probability of having COVID-19 pneumonia for each Model for possible Early COvid-19 Recognition (MECOR) Score value. In conclusion, our model could provide a simple, rapid, and cheap tool for prompt COVID-19 diagnostic triage in patients with CAP. The actual effectiveness should be evaluated in further, prospective studies also involving COVID-19 patients with negative nasopharyngeal swabs.