Species differences in plasma protein binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease inhibitor nirmatrelvir.

Plasma protein binding (PPB) studies on the SARS-CoV-2 main protease inhibitor nirmatrelvir revealed considerable species differences primarily in dog and rabbit, which prompted further investigations into the biochemical basis for these differences.The unbound fraction (fu) of nirmatrelvir in dog and rabbit plasma was concentration (2-200 µM)-dependent (dog fu,p 0.024-0.69, rabbit fu,p 0.010-0.82). Concentration (0.1-100 µM)-dependent binding in serum albumin (SA) (fu,SA 0.040-0.82) and alpha-1-acid glycoprotein (AAG) (fu,AAG 0.050-0.64) was observed in dogs. Nirmatrelvir showed minimal binding to rabbit SA (1-100 µM: fu,SA 0.70-0.79), while binding to rabbit AAG was concentration-dependent (0.1-100 µM: fu,AAG 0.024-0.66). In contrast, nirmatrelvir (2 µM) revealed minimal binding (fu,AAG 0.79-0.88) to AAG from rat and monkeys. Nirmatrelvir showed minimal-to-moderate binding to SA (1-100 µM; fu,SA 0.70-1.0) and AAG (0.1-100 µM; fu,AAG 0.48-0.58) from humans across tested concentrations.Nirmatrelvir molecular docking studies using published crystal structures and homology models of human and preclinical species SA and AAG were used to rationalise the species differences to plasma proteins. This suggested that species differences in PPB are primarily driven by molecular differences in albumin and AAG resulting in differences in binding affinity.

Clathrin-Mediated Albumin Clearance in Alveolar Epithelial Cells of Murine Precision-Cut Lung Slices.

A hallmark of acute respiratory distress syndrome (ARDS) is an accumulation of protein-rich alveolar edema that impairs gas exchange and leads to worse outcomes. Thus, understanding the mechanisms of alveolar albumin clearance is of high clinical relevance. Here, we investigated the mechanisms of the cellular albumin uptake in a three-dimensional culture of precision-cut lung slices (PCLS). We found that up to 60% of PCLS cells incorporated labeled albumin in a time- and concentration-dependent manner, whereas virtually no uptake of labeled dextran was observed. Of note, at a low temperature (4 °C), saturating albumin receptors with unlabeled albumin and an inhibition of clathrin-mediated endocytosis markedly decreased the endocytic uptake of the labeled protein, implicating a receptor-driven internalization process. Importantly, uptake rates of albumin were comparable in alveolar epithelial type I (ATI) and type II (ATII) cells, as assessed in PCLS from a SftpcCreERT2/+: tdTomatoflox/flox mouse strain (defined as EpCAM+CD31-CD45-tdTomatoSPC-T1α+ for ATI and EpCAM+CD31-CD45-tdTomatoSPC+T1α- for ATII cells). Once internalized, albumin was found in the early and recycling endosomes of the alveolar epithelium as well as in endothelial, mesenchymal, and hematopoietic cell populations, which might indicate transcytosis of the protein. In summary, we characterize albumin uptake in alveolar epithelial cells in the complex setting of PCLS. These findings may open new possibilities for pulmonary drug delivery that may improve the outcomes for patients with respiratory failure.

Investigation of inflammation, oxidative stress, and DNA damage in COVID-19 patients.

COVID-19 disease, which spreads worldwide, is a disease characterized by widespread inflammation and affects many organs, especially the lungs. The resulting inflammation can lead to reactive oxygen radicals, leading to oxidative DNA damage. The pneumonia severity of 95 hospitalized patients with positive RT-PCR test was determined and divided into three groups: mild, moderate, and severe/critical. Inflammation markers (neutrophil-lymphocyte ratio, serum reactive protein, procalcitonin, etc.) were determined, and IL-10 and IFN-γ measurements were analyzed using the enzyme-linked immunosorbent assay method. In evaluating oxidative damage, total thiol, native thiol, disulfide, and ischemia-modified albumin (IMA) levels were determined by measuring spectrophotometrically. The comet assay method's percentage of tail DNA obtained was used to determine oxidative DNA damage. As a result, when the mild and severe/critical groups were compared, we found that total thiol, native thiol, and disulfide levels decreased significantly in the severe/critical group due to the increase in inflammation markers and cytokine levels (p < 0.05). We could not detect any significance in IMA levels between the groups (p > 0.05). At the same time, we determined an increase in the tail DNA percent level, that is, DNA damage, due to the increased oxidative effect. As a result, we determined that inflammation and oxidative stress increased in patients with severe pneumonia, and there was DNA damage in these patients.

SARS-CoV-2 Spike Protein Binding of Glycated Serum Albumin-Its Potential Role in the Pathogenesis of the COVID-19 Clinical Syndromes and Bias towards Individuals with Pre-Diabetes/Type 2 Diabetes and Metabolic Diseases.

The immune response to SARS-CoV-2 infection requires antibody recognition of the spike protein. In a study designed to examine the molecular features of anti-spike and anti-nucleocapsid antibodies, patient plasma proteins binding to pre-fusion stabilised complete spike and nucleocapsid proteins were isolated and analysed by matrix-assisted laser desorption ionisation-time of flight (MALDI-ToF) mass spectrometry. Amongst the immunoglobulins, a high affinity for human serum albumin was evident in the anti-spike preparations. Careful mass comparison revealed the preferential capture of advanced glycation end product (AGE) forms of glycated human serum albumin by the pre-fusion spike protein. The ability of bacteria and viruses to surround themselves with serum proteins is a recognised immune evasion and pathogenic process. The preference of SARS-CoV-2 for AGE forms of glycated serum albumin may in part explain the severity and pathology of acute respiratory distress and the bias towards the elderly and those with (pre)diabetic and atherosclerotic/metabolic disease.

Nutritional biomarkers as predictors of clinical outcomes between COVID-19 severity groups in a tertiary government hospital.

BACKGROUND: Malnutrition, as defined by the World Health Organization (WHO), includes undernutrition. In the Philippines, malnutrition is common due to several factors. The nutritional biomarkers can be used as an alternative indicator of dietary intake and nutritional status that can detect deficiencies in support to clinical management of COVID-19 patients. Apart from that, biomarkers are potentially useful for screening, clinical management, and prevention of serious complications of COVID-19 patients. Serum albumin, c-reactive protein (CRP), leukocyte count, lymphocyte count, blood urea nitrogen (BUN) to compute the nutritional prognostic indices (Prognostic nutritional index (PNI) score, BUN/Albumin ratio (BAR) and CRP/Albumin ratio (CAR). OBJECTIVES: To compare the nutritional biomarkers of patients with COVID-19 based on case severity and determine the nutritional prognostic indices and associate to patients' clinical outcome during hospital stay. METHODS: A single center, cross-sectional study was performed between June 2021 to August 2021 in a COVID-19 designated referral center in CALABARZON which comprised of 167 patients as part of the study. Clinicodemographic profile including patients' age, sex, co-morbidities, weight, height, laboratory, and serum biomarkers during the first 48 h of admission (serum albumin, leukocyte count, lymphocytes count, CRP, and BUN) were collated wherein the nutritional prognostic indices were computed and analyzed. Clinical outcomes of the patients were based on the patients' final diagnoses (recovered, length of hospital stay (LOHS), progression of severity and mortality). RESULTS: 167 non-critically ill COVID-19 patients were included in the analysis, of which 52.7% are admitted under the COVID-19 severe group and 47.3% for COVID-19 Mild/Moderate. Mostly are male (53.3%) with an average body mass index (BMI) of 24.26 (SD = 3.52) and have hypertension (55.1%) and diabetes (42.5%). Among the nutritional biomarker, albumin (p = 0.028; p = 0.004), total lymphocyte count (TLC) (p = 0.013; p = 0.005) and BUN (p = 0.001; p=<0.001) were shown to be significantly associated with progression of severity and mortality. Univariate logistic regression analysis showed the following nutritional prognostic score were correlated. (1.) progression of COVID-19 severity: PNI score (OR 0.928, 95% CI 0.886, 0.971, p=<0.001), and BAR value (OR 1.130, 95% CI 1.027, 1.242, p = 0.012); (2.) Mortality: PNI score (OR 0.926, 95% CI 0.878, 0.977, p = 0.005), CAR (OR 1.809, 95% CI 1.243, 2.632, p = 0.002), and BAR (OR 1.180, 95% CI 1.077, 1.292, p=<0.001). The average LOHS of COVID-19 patients was 12 days (SD = 7.72). However, it does not show any significant correlation between any nutritional biomarker, prognostic indices and LOHS. CONCLUSION: This study demonstrated that deranged level of nutritional biomarkers can affect patient's COVID-19 severity and associated with patient's clinical outcome. Low albumin (≤2.5  g/dL), low level of TLC (≤1500 cells/mm3), elevated BUN (≥7.1 mmol/L) are associated with patient's case severity progression and mortality while low PNI score (<42.49), high BAR value (≥2.8) and CAR value (≥2.04) provided an important nutritional prognostic information and could predict mortality which can be a useful parameter in admission, hence it is recommended to screen all COVID-19 patients to reduce mortality.

Effect of the COVID-19 pandemic on the oral health and nutritional status of Japanese older adults who underwent total hip or knee arthroplasty: A 3-year single-institution retrospective cohort study.

The coronavirus disease 2019 (COVID-19) pandemic affected the physical and mental health, socioeconomic status, and community behavior of people worldwide. The aim of this retrospective cohort study was to analyze the impact of the COVID-19 pandemic on the oral health and nutritional status of Japanese older adults based on the results of preoperative assessment in patients who underwent total hip or knee arthroplasty under general anesthesia. This study included older adults (≧65 years) who underwent total hip or knee arthroplasty in whom orthopantomography was performed for preoperative oral health assessment, during January 2019 to December 2021. Gender, age, number of family members living together, number of teeth, body mass index, and serum total protein and serum albumin levels were collected for analysis of this study. A total of 201 patients aged 65 to 89 years participated in the study. While the COVID-19 pandemic has had no impact on the oral health status, there has been a drop in serum albumin level from the results of multivariable-adjusted regression analysis considering age, gender, number of family members, and time. The COVID-19 pandemic has affected the serum albumin level of Japanese orthopedic patients aged 65 years or older.

The Contribution of Diet Therapy and Probiotics in the Treatment of Sarcopenia Induced by Prolonged Immobilization Caused by the COVID-19 Pandemic.

The prolonged immobilization associated with COVID-19 infection and the restrictions imposed by the pandemic have determined major changes in physical activity and eating habits, with a negative impact on physical performance. This study monitored non-pharmacological interventions (diet therapy and probiotics) in managing sarcopenia for patients with recent SARS-CoV-2 history (14 days). A prospective study was performed on 200 patients (between December 2020-December 2021), with SPPB score < 9, randomly divided into: Group K-DP (93 patients) with dietary therapy (protein 1.2-1.5 g/kg) and probiotics for two months; and Group K-non-DP (107 patients) without diet therapy and probiotics. All patients were included in a specific physical training program (40 min), three sessions per week. Skeletal muscle index (SMI), serum albumin, and hemoglobin were determined. The SMI was initially low for both groups without significant statistical differences (6.5 ± 0.52 kg/m2 for Group K-non-DP vs. 6.7 ± 0.57 Kg/m2 for Group K-DP, p = 0.135). After two months, significant difference between initial and final SMI values was determined for Group K-DP (6.92 ± 0.50 kg/m2 vs. 6.77 ± 0.56 kg/m2, p = 0.048). In Group K-DP, at end of study, were more patients with normal SMI (n = 32 → N = 70) values (p < 0.001) and fewer sarcopenia patients (p < 0.001). The initial serum albumin means values in the two groups (Group K-non-DP, 4.17 ± 1.04 g/dL, and Group K-DP, 3.95 ± 0.98 g/dL) were not statistically significantly different (p = 0.122). The hemoglobin level improved significantly following a hyper protein diet enriched with pro-biotics (p = 0.003). Diet therapy, consisting of increased protein intake and specific probiotics and specific physical therapy, demonstrated superiority in improving the functional status of patients with recent COVID-19 infection.

Complementary Sets of Autoantibodies Induced by SARS-CoV-2, Adenovirus and Bacterial Antigens Cross-React with Human Blood Protein Antigens in COVID-19 Coagulopathies.

COVID-19 patients often develop coagulopathies including microclotting, thrombotic strokes or thrombocytopenia. Autoantibodies are present against blood-related proteins including cardiolipin (CL), serum albumin (SA), platelet factor 4 (PF4), beta 2 glycoprotein 1 (ß2GPI), phosphodiesterases (PDE), and coagulation factors such as Factor II, IX, X and von Willebrand factor (vWF). Different combinations of autoantibodies associate with different coagulopathies. Previous research revealed similarities between proteins with blood clotting functions and SARS-CoV-2 proteins, adenovirus, and bacterial proteins associated with moderate-to-severe COVID-19 infections. This study investigated whether polyclonal antibodies (mainly goat and rabbit) against these viruses and bacteria recognize human blood-related proteins. Antibodies against SARS-CoV-2 and adenovirus recognized vWF, PDE and PF4 and SARS-CoV-2 antibodies also recognized additional antigens. Most bacterial antibodies tested (group A streptococci [GAS], staphylococci, Escherichia coli [E. coli], Klebsiella pneumoniae, Clostridia, and Mycobacterium tuberculosis) cross-reacted with CL and PF4. while GAS antibodies also bound to F2, Factor VIII, Factor IX, and vWF, and E. coli antibodies to PDE. All cross-reactive interactions involved antibody-antigen binding constants smaller than 100 nM. Since most COVID-19 coagulopathy patients display autoantibodies against vWF, PDE and PF4 along with CL, combinations of viral and bacterial infections appear to be necessary to initiate their autoimmune coagulopathies.

Low serum albumin: A neglected predictor in patients with cardiovascular disease.

Albumin, the most abundant circulating protein in blood, is an essential protein which binds and transports various drugs and substances, maintains the oncotic pressure of blood and influences the physiological function of the circulatory system. Albumin also has anti-inflammatory, antioxidant, and antithrombotic properties. Evidence supports albumin's role as a strong predictor of cardiovascular (CV) risk in several patient groups. Its protective role extends to those with coronary artery disease, heart failure, hypertension, atrial fibrillation, peripheral artery disease or ischemic stroke, as well as those undergoing revascularization procedures or with aortic stenosis undergoing transcatheter aortic valve replacement, and patients with congenital heart disease and/or endocarditis. Hypoalbuminemia is a strong prognosticator of increased all-cause and CV mortality according to several cohort studies and meta-analyses in hospitalized and non-hospitalized patients with or without comorbidities. Normalization of albumin levels before discharge lowers mortality risk, compared with hypoalbuminemia before discharge. Modified forms of albumin, such as ischemia modified albumin, also has prognostic value in patients with coronary or peripheral artery disease. When albumin is combined with other risk factors, such as uric acid or C-reactive protein, the prognostic value is enhanced. Although albumin supplementation may be a plausible approach, its efficacy has not been established and in patients with hypoalbuminemia, priority is focused on diagnosing and managing the underlying condition. The CV effects of hypoalbuminemia and relevant issues are considered in this review. Large cohort studies and meta-analyses are tabulated and the physiologic effects of albumin and the deleterious effects of low albumin are pictorially illustrated.

Mortality Predictors in Severe SARS-CoV-2 Infection.

Background and Objectives: The severe forms of SARS-CoV-2 pneumonia are associated with acute hypoxic respiratory failure and high mortality rates, raising significant challenges for the medical community. The objective of this paper is to present the importance of early quantitative evaluation of radiological changes in SARS-CoV-2 pneumonia, including an alternative way to evaluate lung involvement using normal density clusters. Based on these elements we have developed a more accurate new predictive score which includes quantitative radiological parameters. The current evolution models used in the evaluation of severe cases of COVID-19 only include qualitative or semi-quantitative evaluations of pulmonary lesions which lead to a less accurate prognosis and assessment of pulmonary involvement. Materials and Methods: We performed a retrospective observational cohort study that included 100 adult patients admitted with confirmed severe COVID-19. The patients were divided into two groups: group A (76 survivors) and group B (24 non-survivors). All patients were evaluated by CT scan upon admission in to the hospital. Results: We found a low percentage of normal lung densities, PaO2/FiO2 ratio, lymphocytes, platelets, hemoglobin and serum albumin associated with higher mortality; a high percentage of interstitial lesions, oxygen flow, FiO2, Neutrophils/lymphocytes ratio, lactate dehydrogenase, creatine kinase MB, myoglobin, and serum creatinine were also associated with higher mortality. The most accurate regression model included the predictors of age, lymphocytes, PaO2/FiO2 ratio, percent of lung involvement, lactate dehydrogenase, serum albumin, D-dimers, oxygen flow, and myoglobin. Based on these parameters we developed a new score (COV-Score). Conclusions: Quantitative assessment of lung lesions improves the prediction algorithms compared to the semi-quantitative parameters. The cluster evaluation algorithm increases the non-survivor and overall prediction accuracy.COV-Score represents a viable alternative to current prediction scores, demonstrating improved sensitivity and specificity in predicting mortality at the time of admission.

Serum Albumin in Health and Disease: Esterase, Antioxidant, Transporting and Signaling Properties.

Being one of the main proteins in the human body and many animal species, albumin plays a decisive role in the transport of various ions-electrically neutral and charged molecules-and in maintaining the colloidal osmotic pressure of the blood. Albumin is able to bind to almost all known drugs, as well as many nutraceuticals and toxic substances, largely determining their pharmaco- and toxicokinetics. Albumin of humans and respective representatives in cattle and rodents have their own structural features that determine species differences in functional properties. However, albumin is not only passive, but also an active participant of pharmacokinetic and toxicokinetic processes, possessing a number of enzymatic activities. Numerous experiments have shown esterase or pseudoesterase activity of albumin towards a number of endogeneous and exogeneous esters. Due to the free thiol group of Cys34, albumin can serve as a trap for reactive oxygen and nitrogen species, thus participating in redox processes. Glycated albumin makes a significant contribution to the pathogenesis of diabetes and other diseases. The interaction of albumin with blood cells, blood vessels and tissue cells outside the vascular bed is of great importance. Interactions with endothelial glycocalyx and vascular endothelial cells largely determine the integrative role of albumin. This review considers the esterase, antioxidant, transporting and signaling properties of albumin, as well as its structural and functional modifications and their significance in the pathogenesis of certain diseases.

Prognostic indicators associated with progresses of severe dengue.

BACKGROUND: Dengue usually progress abnormally, especially in the critical phase. The main causes of death were shock, severe bleeding and organ failure. The aim of our study was to evaluate prognostic indicators of severe dengue according to the phases of the disease progression. METHODS: A cross-sectional study was conducted from July to December 2017 at the National Hospital for Tropical Diseases and the Hospital for Tropical Diseases of Ho Chi Minh City. 326 patients, aged 6 years and over, including 99/326 patients with severe dengue and 227/326 patients with non-severe dengue, hospitalized in the first 3 days of illness, confirmed Dengue virus by the RT-PCR assay have been registered for the study. Clinical manifestations were monitored daily. The hematocrit, white blood cells, platelet, serum albumin, ALT, AST, bilirubin, prothrombin time (PT%, PTs), fibrinogen, aPTT, INR and creatinine were evaluated at two times: febrile phase and critical phase. RESULTS: Independent factors associated with severe dengue were identified on multivariate logistic regression models. During the first 3 days of the disease, the prognostic indicators were platelet count ≤ 100 G/L (OR = 2.2; 95%CI: 1.2-3.9), or serum albumin < 35 g/L (OR = 3.3; 95%CI: 1.8-6.1). From day 4-6, the indicator were AST > 400 U/L (OR = 3.0; 95%CI: 1.1-7.9), ALT > 400 U/L (OR = 6.6; 95%CI: 1.7-24.6), albumin < 35 g/L (OR = 3.0; 95%CI: 1.5-5.9), and bilirubin total >17 µmol/L (OR = 4.6; 95%CI: 2.0-10.4). CONCLUSION: To predict the risk of patients with severe dengue, prognostic laboratory indicators should be indicated consistent with the progression of the disease. During the first 3 days of illness, prognostic indicators should be platelet count, or serum albumin. From the 4th - 6th day of illness, prognostic indicators should be AST, ALT, albumin, or bilirubin total.

Factors predictive of anti-spike antibody titers after COVID-19 vaccination in hemodialysis patients.

BACKGROUND: Hemodialysis (HD) patients have a high prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and mortality, but they may have a weak response to coronavirus disease 2019 (COVID-19) vaccines. OBJECTIVES: This study aimed to evaluate factors predictive of humoral response in HD patients vaccinated against SARS-CoV-2 infection. MATERIAL AND METHODS: This is a 2-center observational study including HD patients who received the BNT162b2 mRNA vaccine followed by serological measurements 20 days and 4 weeks after the 1st and 2nd dose, respectively. Healthy controls were included. Anti-spike antibody was measured using the chemiluminescent immunoassay (CLIA) method. The quantile regression analysis was performed to assess factors associated with anti-spike antibody titers. RESULTS: Seventy-two HD patients and 22 healthy controls were included. Mean age of dialysis patients and controls was 72.5 ±11.5 years and 45.7 ±17.4 years, respectively. In the HD group, median levels of anti-spike antibody were 3 (interquartile range (IQR): 0.5-26) UI/mL and 391 (IQR: 55-1642) UI/mL after the 1st and 2nd dose, respectively, with response rates of 62.5% and 96.7%. The median level of the anti-spike antibody after the 1st dose in previously infected patients was 8571 (IQR: 2586-19147) UI/mL. There was a significant correlation between anti-spike antibody levels after the 2nd dose and age and anti-hepatitis B surface (HBs) antibody and serum albumin levels (Spearman's rho: r = -0.289, p < 0.001; r = 0.357, p = 0.027; r = 0.317; p = 0.026, respectively). The regression analysis showed a significant association of previous infection and anti-Hbs antibody level with anti-spike antibody level after the 1st dose of vaccine (p < 0.001). After a 5-month follow-up, 2 vaccinated patients contracted COVID-19. CONCLUSIONS: This study showed a response rate of 96.7% to 2 doses of BNT162b2 mRNA vaccine in HD patients and 100% to a single dose in previously infected patients. The level of anti-spike antibody can be predicted by age, anti-Hbs antibodies, serum albumin, and previous infection. Despite the immunization of patients, preventive measures should be maintained in all dialysis units.

COVID-19 Infection in Kidney Transplant Recipients: A Single Center Experience.

BACKGROUND: Kidney transplant recipients appear to be particularly high risk for critical COVID-19 illness owing to chronic immunosuppression and coexisting conditions. The aim of this study is to present the clinical characteristics and outcomes of our hospital's kidney transplant recipients who were hospitalized due to COVID-19 infection. METHODS: In our retrospective observational study of COVID-19 PCR-positive patients, 31 of them were hospitalized with COVID-19 pneumonia and they were evaluated using demographics, laboratory data, treatment, and outcome. The prognostic nutritional index (PNI), which is calculated using the serum albumin concentration and total lymphocytic count, was also evaluated. The baseline immunosuppressive therapy of patients at the time of admission and the treatments they received during their hospitalization were recorded. All patients were treated with favipiravir. RESULTS: Of the 31 renal transplant patients with COVID-19 pneumonia, 20 were male and the mean age was 52.7 ± 13.4. Nine (29%) of the patients died. All patients were treated with favipiravir for 5 days; laboratory tests were recorded before and after treatment. The mean PNI of the patients who survived was higher than the patients who died. CONCLUSIONS: The 9 patients who died had lower PNI and higher neutrophil-to-lymphocyte ratio (NLR), creatinine, l-lactate dehydrogenase (LDH), ferritin, and C-reactive protein (CRP) levels. Hospitalized kidney transplant recipients with COVID-19 have higher rates of mortality. The PNI exhibited good predictive performance and may be a useful clinical marker that can be used for estimating survival in COVID-19 patients.

Psychiatric comorbidities and dehydration are more common in children admitted to the emergency department for eating disorders in the COVID-19 era.

PURPOSE: Since the beginning of COVID-19 pandemic, social distancing and home confinement had a significant impact on children, especially on those with eating disorders (ED). The primary objective of this retrospective study was to describe and analyze the demographic and clinical profiles of children presenting with ED during the COVID-19 pandemic. METHODS: We conducted a retrospective review of clinical charts of patients with ED younger than 18 years who accessed the emergency department of the Bambino Gesù Children's Hospital, Rome, between March 2019 and March 2021. Of these, we reported and compared the demographic, clinical and laboratory data before and after the COVID-19 pandemic and looked for predictors of ED severity. RESULTS: A total of 211 admissions for ED were recorded. The patients, mostly females (86.3%) were on average 14.1 years old. The mean weight loss on admission was 11 kg. Bradycardia was observed in 31.3% of the study sample. 16.6% of patients had an associated psychiatric disorder and 60.2% required psychotropic drugs. 68.7% of the patients required hospitalization. Respectively, 96 and 115 patients were admitted before and during the COVID-19 pandemic. The latter were hospitalized more (78.3 vs 57.3%; p = 0.001), yet for less time (19 vs 26 days; p = 0.004), had a higher mean serum creatinine (0.68 vs 0.47; p < 0.001) and were more frequently diagnosed with an associated psychiatric disorder (23.5 vs 8.3%; p = 0.003). CONCLUSION: Our study shows a significant increase of hospitalizations of children with ED during the COVID-19 pandemic, along with a shorter length of stay, more psychiatric comorbidities, and some distinctive features at the laboratory work-up, such as an increase of serum creatinine and/or a reduction of serum albumin. LEVEL OF EVIDENCE: III, evidence obtained from well-designed cohort or case-control analytic studies.

The ADA (Age-D-Dimer-Albumin) Score to Predict Thrombosis in SARS-CoV-2.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-related pneumonia is associated with venous and arterial thrombosis. Aim of the study was to find out a new score for predicting thrombosis in patients with SARS-CoV-2. METHODS: We included a cohort of 674 patients affected by SARS-CoV-2, not requiring intensive care units, and followed-up during the hospitalization until discharge. Routine analyses performed at in-hospital admission included also serum albumin and D-dimer while arterial and venous thromboses were the endpoints of the study. RESULTS: During the follow-up, 110 thrombotic events were registered; patients with thrombotic events were older and had lower albumin and higher D-dimer, compared with thrombotic event-free ones. On multivariable logistic regression with step-by-step procedure age, serum albumin, and D-dimer were independently associated with thrombotic events. The linear combination of age, D-dimer, and albumin allowed to build-up the ADA (age-D-dimer-albumin) score, whose area under the curve (AUC) was 0.752 (95% confidence interval [CI], 0.708-0.795). ADA score was internally validated by bootstrap sampling procedure giving an AUC of 0.752 (95% CI: 0.708-0.794). CONCLUSION: Combination of age, D-dimer, and albumin in the ADA score allows identifying SARS-CoV-2 patients at higher risk of thrombotic events.

Evidence for a semisolid phase state of aerosols and droplets relevant to the airborne and surface survival of pathogens.

The phase state of respiratory aerosols and droplets has been linked to the humidity-dependent survival of pathogens such as SARS-CoV-2. To inform strategies to mitigate the spread of infectious disease, it is thus necessary to understand the humidity-dependent phase changes associated with the particles in which pathogens are suspended. Here, we study phase changes of levitated aerosols and droplets composed of model respiratory compounds (salt and protein) and growth media (organic-inorganic mixtures commonly used in studies of pathogen survival) with decreasing relative humidity (RH). Efflorescence was suppressed in many particle compositions and thus unlikely to fully account for the humidity-dependent survival of viruses. Rather, we identify organic-based, semisolid phase states that form under equilibrium conditions at intermediate RH (45 to 80%). A higher-protein content causes particles to exist in a semisolid state under a wider range of RH conditions. Diffusion and, thus, disinfection kinetics are expected to be inhibited in these semisolid states. These observations suggest that organic-based, semisolid states are an important consideration to account for the recovery of virus viability at low RH observed in previous studies. We propose a mechanism in which the semisolid phase shields pathogens from inactivation by hindering the diffusion of solutes. This suggests that the exogenous lifetime of pathogens will depend, in part, on the organic composition of the carrier respiratory particle and thus its origin in the respiratory tract. Furthermore, this work highlights the importance of accounting for spatial heterogeneities and time-dependent changes in the properties of aerosols and droplets undergoing evaporation in studies of pathogen viability.