Investigation of acute-phase protein concentrations in healthy and various diseased cats.

This study aimed to evaluate the concentrations of α1-acid glycoprotein (AGP), haptoglobin (Hp), serum amyloid-A (SAA) and ceruloplasmin (Cp) in healthy and various diseased cats and establish reference intervals (RIs) for these acute phase proteins (APPs) in healthy cats. The animal material of the study consisted of 40 healthy cats and 152 cats with various diseases. The serum APPs in the diseased group were higher than those in the healthy group, and age affected Cp concentration in healthy cats. Also, the systemic inflammatory response syndrome (SIRS) positive (+) group had significantly higher AGP concentrations than the SIRS negative (-) group. In conclusion, this study contributes to the limited number of studies on RIs in serum APPs concentrations in healthy cats. The results of this study suggest that APPs are valuable diagnostic tools for identifying the inflammatory processes of various diseases, and AGP concentration could help determine the severity of the inflammatory condition.

AA-amyloidosis in cats (Felis catus) housed in shelters.

Systemic AA-amyloidosis is a protein-misfolding disease characterized by fibril deposition of serum amyloid-A protein (SAA) in several organs in humans and many animal species. Fibril deposits originate from abnormally high serum levels of SAA during chronic inflammation. A high prevalence of AA-amyloidosis has been reported in captive cheetahs and a horizontal transmission has been proposed. In domestic cats, AA-amyloidosis has been mainly described in predisposed breeds but only rarely reported in domestic short-hair cats. Aims of the study were to determine AA-amyloidosis prevalence in dead shelter cats. Liver, kidney, spleen and bile were collected at death in cats from 3 shelters. AA-amyloidosis was scored. Shedding of amyloid fibrils was investigated with western blot in bile and scored. Descriptive statistics were calculated. In the three shelters investigated, prevalence of AA-amyloidosis was 57.1% (16/28 cats), 73.0% (19/26) and 52.0% (13/25), respectively. In 72.9% of cats (35 in total) three organs were affected concurrently. Histopathology and immunofluorescence of post-mortem extracted deposits identified SAA as the major protein source. The duration of stay in the shelters was positively associated with a histological score of AA-amyloidosis (B = 0.026, CI95% = 0.007-0.046; p = 0.010). AA-amyloidosis was very frequent in shelter cats. Presence of SAA fragments in bile secretions raises the possibility of fecal-oral transmission of the disease. In conclusion, AA-amyloidosis was very frequent in shelter cats and those staying longer had more deposits. The cat may represent a natural model of AA-amyloidosis.

Elevated Serum Amyloid A Levels Contribute to Increased Platelet Adhesion in COVID-19 Patients.

Coronavirus disease-19 (COVID-19) patients are prone to thrombotic complications that may increase morbidity and mortality. These complications are thought to be driven by endothelial activation and tissue damage promoted by the systemic hyperinflammation associated with COVID-19. However, the exact mechanisms contributing to these complications are still unknown. To identify additional mechanisms contributing to the aberrant clotting observed in COVID-19 patients, we analyzed platelets from COVID-19 patients compared to those from controls using mass spectrometry. We identified increased serum amyloid A (SAA) levels, an acute-phase protein, on COVID-19 patients' platelets. In addition, using an in vitro adhesion assay, we showed that healthy platelets adhered more strongly to wells coated with COVID-19 patient serum than to wells coated with control serum. Furthermore, inhibitors of integrin aIIbß3 receptors, a mediator of platelet-SAA binding, reduced platelet adhesion to recombinant SAA and to wells coated with COVID-19 patient serum. Our results suggest that SAA may contribute to the increased platelet adhesion observed in serum from COVID-19 patients. Thus, reducing SAA levels by decreasing inflammation or inhibiting SAA platelet-binding activity might be a valid approach to abrogate COVID-19-associated thrombotic complications.

HDL proteome remodeling associates with COVID-19 severity.

BACKGROUND: Besides the well-accepted role in lipid metabolism, high-density lipoprotein (HDL) also seems to participate in host immune response against infectious diseases. OBJECTIVE: We used a quantitative proteomic approach to test the hypothesis that alterations in HDL proteome associate with severity of Coronavirus disease 2019 (COVID-19). METHODS: Based on clinical criteria, subjects (n=41) diagnosed with COVID-19 were divided into two groups: a group of subjects presenting mild symptoms and a second group displaying severe symptoms and requiring hospitalization. Using a proteomic approach, we quantified the levels of 29 proteins in HDL particles derived from these subjects. RESULTS: We showed that the levels of serum amyloid A 1 and 2 (SAA1 and SAA2, respectively), pulmonary surfactant-associated protein B (SFTPB), apolipoprotein F (APOF), and inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) were increased by more than 50% in hospitalized patients, independently of sex, HDL-C or triglycerides when comparing with subjects presenting only mild symptoms. Altered HDL proteins were able to classify COVID-19 subjects according to the severity of the disease (error rate 4.9%). Moreover, apolipoprotein M (APOM) in HDL was inversely associated with odds of death due to COVID-19 complications (odds ratio [OR] per 1-SD increase in APOM was 0.27, with 95% confidence interval [CI] of 0.07 to 0.72, P=0.007). CONCLUSION: Our results point to a profound inflammatory remodeling of HDL proteome tracking with severity of COVID-19 infection. They also raise the possibility that HDL particles could play an important role in infectious diseases.

Blood fibrocytes are associated with severity and prognosis in COVID-19 pneumonia.

Increased blood fibrocytes are associated with a poor prognosis in fibrotic lung diseases. We aimed to determine whether the percentage of circulating fibrocytes could be predictive of severity and prognosis during coronavirus disease 2019 (COVID-19) pneumonia. Blood fibrocytes were quantified by flow cytometry as CD45+/CD15-/CD34+/collagen-1+ cells in patients hospitalized for COVID-19 pneumonia. In a subgroup of patients admitted in an intensive care unit (ICU), fibrocytes were quantified in blood and bronchoalveolar lavage (BAL). Serum amyloid P (SAP), transforming growth factor-ß1 (TGF-ß1), CXCL12, CCL2, and FGF2 concentrations were measured. We included 57 patients in the hospitalized group (median age = 59 yr [23-87]) and 16 individuals as healthy controls. The median percentage of circulating fibrocytes was higher in the patients compared with the controls (3.6% [0.2-9.2] vs. 2.1% [0.9-5.1], P = 0.04). Blood fibrocyte count was lower in the six patients who died compared with the survivors (1.6% [0.2-4.4] vs. 3.7% [0.6-9.2], P = 0.02). Initial fibrocyte count was higher in patients showing a complete lung computed tomography (CT) resolution at 3 mo. Circulating fibrocyte count was decreased in the ICU group (0.8% [0.1-2.0]), whereas BAL fibrocyte count was 6.7% (2.2-15.4). Serum SAP and TGF-ß1 concentrations were increased in hospitalized patients. SAP was also increased in ICU patients. CXCL12 and CCL2 were increased in ICU patients and negatively correlated with circulating fibrocyte count. We conclude that circulating fibrocytes were increased in patients hospitalized for COVID-19 pneumonia, and a lower fibrocyte count was associated with an increased risk of death and a slower resolution of lung CT opacities.

Serum amyloid A concentrations, COVID-19 severity and mortality: An updated systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: An excessive inflammatory response in patients with coronavirus disease 2019 (COVID-19) is associated with high disease severity and mortality. Specific acute phase reactants might be useful for risk stratification. A systematic review and meta-analysis was conducted of studies on serum amyloid A (SAA) in patients with COVID-19. METHODS: The PubMed, Web of Science, and Scopus databases were searched, covering the period January 2020 to December 2020, for studies reporting SAA concentrations, COVID-19 severity, and survival status. RESULTS: Nineteen studies involving 5617 COVID-19 patients were included in the meta-analysis. Pooled results showed that SAA concentrations were significantly higher in patients with severe disease and non-survivors (standard mean difference (SMD) 1.20, 95% confidence interval 0.91-1.49, P < 0.001). Extreme between-study heterogeneity was observed (I2 = 92.4%, P < 0.001). In the sensitivity analysis, the effect size was not significantly affected when each study was removed in turn (range 1.10-1.29). The Begg test (P = 0.030), but not the Egger test (P = 0.385), revealed the presence of publication bias. Pooled SMD values were significantly and positively associated with sex (t = 2.20, P = 0.047) and aspartate aminotransferase (t = 3.44, P = 0.014). CONCLUSIONS: SAA concentrations were significantly and positively associated with higher COVID-19 severity and mortality. This acute phase reactant might assist with risk stratification and monitoring in this group.

Serum Amyloid A in Inflammatory Rheumatic Diseases: A Compendious Review of a Renowned Biomarker.

Serum amyloid A (SAA) is an acute phase protein with a significant importance for patients with inflammatory rheumatic diseases (IRD). The central role of SAA in pathogenesis of IRD has been confirmed by recent discoveries, including its involvement in the activation of the inflammasome cascade and recruitment of interleukin 17 producing T helper cells. Clinical utility of SAA in IRD was originally evaluated nearly half a century ago. From the first findings, it was clear that SAA could be used for evaluating disease severity and monitoring disease activity in patients with rheumatoid arthritis and secondary amyloidosis. However, cost-effective and more easily applicable markers, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), overwhelmed its use in clinical practice. In the light of emerging evidences, SAA has been discerned as a more sensitive biomarker in a wide spectrum of IRD, especially in case of subclinical inflammation. Furthermore, a growing number of studies are confirming the advantages of SAA over many other biomarkers in predicting and monitoring response to biological immunotherapy in IRD patients. Arising scientific discoveries regarding the role of SAA, as well as delineating SAA and its isoforms as the most sensitive biomarkers in various IRD by recently developing proteomic techniques are encouraging the revival of its clinical use. Finally, the most recent findings have shown that SAA is a biomarker of severe Coronavirus disease 2019 (COVID-19). The aim of this review is to discuss the SAA-involving immune system network with emphasis on mechanisms relevant for IRD, as well as usefulness of SAA as a biomarker in various IRD. Therefore, over a hundred original papers were collected through an extensive PubMed and Scopus databases search. These recently arising insights will hopefully lead to a better management of IRD patients and might even inspire the development of new therapeutic strategies with SAA as a target.

Altered high-density lipoprotein composition and functions during severe COVID-19.

Coronavirus disease 2019 (COVID-19) pandemic is affecting millions of patients worldwide. The consequences of initial exposure to SARS-CoV-2 go beyond pulmonary damage, with a particular impact on lipid metabolism. Decreased levels in HDL-C were reported in COVID-19 patients. Since HDL particles display antioxidant, anti-inflammatory and potential anti-infectious properties, we aimed at characterizing HDL proteome and functionality during COVID-19 relative to healthy subjects. HDLs were isolated from plasma of 8 severe COVID-19 patients sampled at admission to intensive care unit (Day 1, D1) at D3 and D7, and from 16 sex- and age-matched healthy subjects. Proteomic analysis was performed by LC-MS/MS. The relative amounts of proteins identified in HDLs were compared between COVID-19 and controls. apolipoprotein A-I and paraoxonase 1 were confirmed by Western-blot analysis to be less abundant in COVID-19 versus controls, whereas serum amyloid A and alpha-1 antitrypsin were higher. HDLs from patients were less protective in endothelial cells stiumalted by TNFα (permeability, VE-cadherin disorganization and apoptosis). In these conditions, HDL inhibition of apoptosis was blunted in COVID-19 relative to controls. In conclusion, we show major changes in HDL proteome and decreased functionality in severe COVID-19 patients.

Serum-soluble ST2 as a novel biomarker reflecting inflammatory status and illness severity in patients with COVID-19.

Aim: The authors studied the role of soluble ST2 (sST2) in COVID-19 and its relationship with inflammatory status and disease severity. Materials & methods: Serum levels of sST2 and interleukin (IL)-33, C-reactive protein (CRP), serum amyloid protein (SAA), IL-6 and procalcitonin (PCT), and T lymphocyte subsets from 80 subjects diagnosed with COVID-19 including 36 mild, 41 severe and three asymptomatic cases were tested. Results: Serum sST2 levels were significantly increased in COVID-19 patients, which were positively correlated with CRP, but negatively correlated with CD4+ and CD8+ T lymphocyte counts. Serum sST2 levels in nonsurviving severe cases were persistently high during disease progression. Conclusion: Serum sST2 level test is helpful for reflecting inflammatory status and illness severity of COVID-19.

Value of chest imaging in the newborn with suspected COVID-19.

OBJECTIVE: This paper presents a newborn (G2P2, gestational age of 39+6 weeks, birth weight of 3,200 g, with normal fetal amniotic fluid) with suspected coronavirus disease 2019 (COVID-19) admitted to our hospital on February 10, 2020, at the birth age of 16 hours and 34 minutes. The Apgar scores at 1 and 5 min were 9 and 10 points, respectively. PATIENTS AND METHODS: The mother of the newborn was exposed to a patient with COVID-19 five days before delivery. The newborn had nausea and vomiting after birth, with feeding intolerance, and full enteral feeding was given on the 6th day after birth. The newborn was in good general condition during the period of hospitalization. RESULTS: The two 2019-nCoV nucleic acid tests of the newborn were negative on the 5th and 7th days after birth. On the 1st and 8th days after birth, typical pulmonary lesions were detected in the newborn by chest CT. Our study supports that chest imaging examination should be actively performed in the newborn even with a negative 2019-nCoV nucleic acid test in cases where a pregnant woman is exposed to a patient with COVID-19 or is confirmed with 2019-nCoV infection. CONCLUSIONS: For newborns with typical pulmonary lesions, strict quarantine measures are suggested if the possibility of COVID-19 cannot be excluded.

Epidemiology and clinical characteristics of 43 COVID-19 patients in Weifang, China.

BACKGROUND: To investigate the epidemiology and clinical characteristics of patients infected with coronavirus disease 2019 (COVID-19) in Weifang, China. METHODS: The demographic data of 43 COVID-19 patients identified in Weifang were used to investigate whether they had traveled to epidemic areas and whether they had close contact with confirmed cases. On admission, patients' symptoms and results of laboratory tests and imaging were analyzed. RESULTS: Among the 43 COVID-19 patients. including 9 third generation infected cases, 16 (37.2%) were imported, who infected the rest. Most cases were middle-aged with approximate sex ratio. A "super spreader", Mr. Zhang made it necessary to quarantine 69 medical personnel. Mr. Zhang directly infected six individuals who, in turn, infected another six individuals. Another patient, Mr. Wang, spread the infection to his five family members at a family gathering. Subsequently, the daughter infected her husband. The most common COVID-19 symptoms were fever, weakness, dry cough, and cough sputum. In most patients, white blood cell counts were not elevated and lymphocyte counts were decreased. Elevated C-reactive protein and serum amyloid A protein (SAA) levels were commonly observed. There was no death among the patients or infection among the medical staff. CONCLUSIONS: The infection by the COVID-19 in Weifang was mostly the result of close contact with imported cases. These circumstances underscore the need to comprehensively strengthen the management for patients to prevent and control the spread of the virus.

Prognostic value of serum amyloid A in patients with COVID-19.

OBJECTIVE: To investigate the prognostic value of serum amyloid A (SAA) in the patients with Corona Virus Disease 2019 (COVID-19). METHODS: The medical data of 89 COVID-19 patients admitted to Renmin Hospital of Wuhan University from January 3, 2020 to February 26, 2020 were collected. Eighty-nine cases were divided into survival group (53 cases) and non-survival group (36 cases) according to the results of 28-day follow-up. The SAA levels of all patients were recorded and compared on 1 day after admission (before treatment) and 3 days, 5 days, and 7 days after treatment. The ROC curve was drawn to analyze the prognosis of patients with COVID-19 by SAA. RESULTS: The difference of comparison of SAA between survival group and non-survival group before treatment was not statistically significant, Z1 = - 1.426, P = 0.154. The Z1 values (Z1 is the Z value of the rank sum test) of the two groups of patients at 3 days, 5 days, and 7 days after treatment were - 5.569, - 6.967, and - 7.542, respectively. The P values were all less than 0.001, and the difference was statistically significant. The ROC curve results showed that SAA has higher sensitivity to the prognostic value of 1 day (before treatment), 3 days, 5 days, and 7 days after treatment, with values of 0.806, 0.972, 0.861, and 0.961, respectively. Compared with SAA on the 7th day and C-reactive protein, leukocyte count, neutrophil count, lymphocyte count, and hemoglobin on the 7th day, the sensitivities were: 96.1%, 83.3%, 88.3%, 83.3%, 67.9%, and 83.0%, respectively, of which SAA has the highest sensitivity. CONCLUSION: SAA can be used as a predictor of the prognosis in patients with COVID-19.

Clinical and epidemiological characteristics of pediatric SARS-CoV-2 infections in China: A multicenter case series.

BACKGROUND: As of April 18, 2020, over 2,000,000 patients had been diagnosed with coronavirus disease-2019 (COVID-19) globally, and more than 140,000 deaths had been reported. The clinical and epidemiological characteristics of adult patients have been documented recently. However, information on pediatric patients is limited. We describe the clinical and epidemiological characteristics of pediatric patients to provide valuable insight into the early diagnosis and assessment of COVID-19 in children. METHODS AND FINDINGS: This retrospective, observational study involves a case series performed at 4 hospitals in West China. Thirty-four pediatric patients with COVID-19 were included from January 27 to February 23, 2020. The final follow-up visit was completed by March 16, 2020. Clinical and epidemiological characteristics were analyzed on the basis of demographic data, medical history, laboratory tests, radiological findings, and treatment information. Data analysis was performed for 34 pediatrics patients with COVID-19 aged from 1 to 144 months (median 33.00, interquartile range 10.00-94.25), among whom 14 males (41%) were included. All the patients in the current study presented mild (18%) or moderate (82%) forms of COVID-19. A total of 48% of patients were noted to be without a history of exposure to an identified source. Mixed infections of other respiratory pathogens were reported in 16 patients (47%). Comorbidities were reported in 6 patients (18%). The most common initial symptoms were fever (76%) and cough (62%). Expectoration (21%), vomiting (12%), and diarrhea (12%) were also reported in a considerable portion of cases. A substantial increase was detected in serum amyloid A for 17 patients (among 20 patients with available data; 85%) and in high-sensitivity C-reactive protein for 17 patients (among 29 patients with available data; 59%), whereas a decrease in prealbumin was noticed in 25 patients (among 32 patients with available data; 78%). In addition, significant increases in the levels of lactate dehydrogenase and α-hydroxybutyrate dehydrogenase were detected in 28 patients (among 34 patients with available data; 82%) and 25 patients (among 34 patients with available data; 74%), respectively. Patchy lesions in lobules were detected by chest computed tomographic scans in 28 patients (82%). Ground-glass opacities, which were a typical feature in adults, were rare in pediatric patients (3%). Rapid radiologic progression and a late-onset pattern of lesions in the lobules were also noticed. Lesions in lobules still existed in 24 (among 32 patients with lesions; 75%) patients that were discharged, although the main symptoms disappeared a few days after treatment. All patients were discharged, and the median duration of hospitalization was 10.00 (8.00-14.25) days. The current study was limited by the small sample size and a lack of dynamic detection of inflammatory markers. CONCLUSIONS: Our data systemically presented the clinical and epidemiological features, as well as the outcomes, of pediatric patients with COVID-19. Stratified analysis was performed between mild and moderate cases. The findings offer new insight into early identification and intervention in pediatric patients with COVID-19.