SARS-CoV-2 multi-antigen protein microarray for detailed characterization of antibody responses in COVID-19 patients

Antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) target multiple epitopes on different domains of the spike protein, and other SARS-CoV-2 proteins. We developed a SARS-CoV-2 multi-antigen protein microarray with the nucleocapsid, spike and its domains (S1, S2), and variants with single (D614G, E484K, N501Y) or double substitutions (N501Y/Deletion69/70), allowing a more detailed high-throughput analysis of the antibody repertoire following infection. The assay was demonstrated to be reliable and comparable to ELISA. We analyzed antibodies from 18 COVID-19 patients and 12 recovered convalescent donors. S IgG level was higher than N IgG in most of the COVID-19 patients, receptor-binding domain of S1 showed high reactivity, but no antibodies were detected against heptad repeat domain 2 of S2. Furthermore, antibodies were detected against S variants with single and double substitutions in COVID-19 patients who were infected with SARS-CoV-2 early in the pandemic. Here we demonstrated that SARS-CoV-2 multi-antigen protein microarray is a powerful tool for detailed characterization of antibody responses, with potential utility in understanding the disease progress and assessing current vaccines and therapies against evolving SARS-CoV-2.

Functional Antibodies in COVID-19 Convalescent Plasma

In the absence of an effective vaccine or monoclonal therapeutic, transfer of convalescent plasma (CCP) was proposed early in the SARS-CoV-2 pandemic as an easily accessible therapy. However, despite the global excitement around this historically valuable therapeutic approach, results from CCP trials have been mixed and highly debated. Unlike other therapeutic interventions, CCP represents a heterogeneous drug. Each CCP unit is unique and collected from an individual recovered COVID-19 patient, making the interpretation of therapeutic benefit more complicated. While the prevailing view in the field would suggest that it is administration of neutralizing antibodies via CCP that centrally provides therapeutic benefit to newly infected COVID-19 patients, many hospitalized COVID-19 patients already possess neutralizing antibodies. Importantly, the therapeutic benefit of antibodies can extend far beyond their simple ability to bind and block infection, especially related to their ability to interact with the innate immune system. In our work we deeply profiled the SARS-CoV-2-specific Fc-response in CCP donors, along with the recipients prior to and after CCP transfer, revealing striking SARS-CoV-2 specific Fc-heterogeneity across CCP units and their recipients. However, CCP units possessed more functional antibodies than acute COVID-19 patients, that shaped the evolution of COVID-19 patient humoral profiles via distinct immunomodulatory effects that varied by pre-existing SARS-CoV-2 Spike (S)-specific IgG titers in the patients. Our analysis identified surprising influence of both S and Nucleocapsid (N) specific antibody functions not only in direct antiviral activity but also in anti-inflammatory effects. These findings offer insights for more comprehensive interpretation of correlates of immunity in ongoing large scale CCP trials and for the design of next generation therapeutic design.

Treatment of Severe COVID-19 with Convalescent Plasma in the Bronx, NYC

Convalescent plasma with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) antibodies (CCP) may hold promise as treatment for Coronavirus Disease 2019 (COVID-19). We compared the mortality and clinical outcome of patients with COVID-19 who received 200mL of CCP with a Spike protein IgG titer [≥]1:2,430 (median 1:47,385) within 72 hours of admission to propensity score-matched controls cared for at a medical center in the Bronx, between April 13 to May 4, 2020. Matching criteria for controls were age, sex, body mass index, race, ethnicity, comorbidities, week of admission, oxygen requirement, D-dimer, lymphocyte counts, corticosteroids, and anticoagulation use. There was no difference in mortality or oxygenation between CCP recipients and controls at day 28. When stratified by age, compared to matched controls, CCP recipients <65 years had 4-fold lower mortality and 4-fold lower deterioration in oxygenation or mortality at day 28. For CCP recipients, pre-transfusion Spike protein IgG, IgM and IgA titers were associated with mortality at day 28 in univariate analyses. No adverse effects of CCP were observed. Our results suggest CCP may be beneficial for hospitalized patients <65 years, but data from controlled trials is needed to validate this finding and establish the effect of ageing on CCP efficacy.

Comparison of Serum Procalcitonin with Ranson, APACHE-II, Glasgow and Balthazar CT Severity Index Scores in Predicting Severity of Acute Pancreatitis / 대한소화기학회지

BACKGROUND/AIMS: The aim of this study is to assess serum procalcitonin (PCT) for early prediction of severe acute pancreatitis compared with multiple scoring systems and biomarkers. METHODS: Forty-four patients with acute pancreatitis confirmed by radiological evidences, laboratory assessments, and clinical manifestation were prospectively enrolled. All blood samples and image studies were obtained within 24 hours of admission. RESULTS: Acute pancreatitis was graded as severe in 19 patients and mild in 25 patients according to the Atlanta criteria. Levels of serum PCT were significantly higher in severe acute pancreatitis (p=0.001). The accuracy of serum PCT as a predicting marker was 77.3%, which was similar to the acute physiology and chronic health examination (APACHE)-II score, worse than the Ranson score (93.2%) and better than the Balthazar CT index (65.9%). The most effective cut-off level of serum PCT was estimated at 1.77 ng/mL (AUC=0.797, 95% CI=0.658-0.935). In comparision to other simple biomarkers, serum PCT had more accurate value (77.3%) than C-reactive protein (68.2%), urea (75.0%) and lactic dehydrogenase (72.7%). Logistic regression analysis revealed that serum PCT has statistical significance in acute severe pancreatitis. Assessment of serum PCT levels and length of hospital stay by simple linear regression analysis revealed effective p-value with low R square level, which could make only possibilty for affection of serum PCT to admission duration (r2=0.127, p=0.021). CONCLUSIONS: Serum PCT was a promising simple biomarker and had similar accuracy of APACHE-II scores as predicting severity of acute pancreatitis.

Glomus Tumor in Stomach: 3 Cases / 대한내과학회지

Glomus tumors originate in modified vascular smooth muscle cells and are most commonly found in the dermis or subcutis but are rarely observed in the stomach. We report three cases of patients who presented with incidental findings of subepithelial tumors in the stomach. One patient showed a positive cushion sign, and the others showed negative cushion signs. Endoscopic ultrasonography (EUS) demonstrated sharply demarcated hypoechoic tumors with internal hyperechoic spots in the fourth layer of the gastric wall and several hypoechoic halos around the tumors. Contrast-enhanced abdominal computerized tomography (CT) showed homogeneous high enhancement of tumors up to the delayed scan, and one case showed calcification in the tumor. For treatment, laparoscopic wedge resections were performed. Histological and immunochemical analysis of the tumor cells were compatible with glomus tumors. These characteristic findings in EUS and CT seem to be useful for the diagnosis of gastric glomus tumors.

A Case of Leiomyosarcoma of the Sigmoid Colon Presenting as Intussusception / 대한소화기내시경학회지

Leiomyosarcomas are malignant tumors of smooth muscle. Leiomyosarcomas of the large intestine are rare, with an incidence of less than 0.1% of all colorectal malignancies. A 70-year-old woman was admitted to the hospital with lower abdominal pain and hematochezia. The abdominal CT scan revealed a solid mass in the sigmoid colon and intussusception with a lead point. Surgical excision of the sigmoid colon mass was performed. The patient was diagnosed with a leiomyosarcoma originating from the sigmoid colon. Few cases of primary sigmoid colon leiomyosarcoma presenting as an intussusception have been reported in the medical literature. We report here on a case of complete surgical resection for a leiomyosarcoma of the sigmoid colon and this presented as intussusception.

Clinical outcome of pegylated interferon and ribavirin therapy for chronic hepatitis C / 대한간학회지

BACKGROUND/AIMS: The purpose of this study is to elucidate the efficacy and safety of combined peginterferon and ribavirin therapy in Korean patients with chronic HCV infection. METHODS: We retrospectively analyzed the clinical records of 84 patients. Thirty five patients with genotype 1 HCV infection were treated with peginterferon alpha-2a 180 microgram/week and ribavirin 1,000-1,200 mg/day for 48 weeks, and 49 patients with genotype non-1 were treated with peginterferon alpha-2a 180 microgram/week and ribavirin 800 mg/day for 24 weeks. RESULTS: An early virologic response was seen in 87.0% of patients with genotype 1 HCV. An end of treatment response (ETR) was seen in 82.6% and 97.6% of patients with genotype 1 and genotype non-1, respectively. An overall sustained virologic response (SVR) was seen in 53 patients (82.8%) of the 64 patients: in 16 (69.6%) of 23 patients with genotype 1 and in 37 (90.2%) of 41 patients with genotype non-1. An end of treatment biochemical response was seen in 58 patients (90.6%) [genotype 1, 20 patients (87.0%); genotype non-1, 38 patients (92.7%)], and a sustained biochemical response was achieved in 49 patients (76.6%) [genotype 1, 14 patients (60.9%); genotype non-1, 35 patients (85.4%)]. Independent factors affecting an SVR were HCV genotype and the baseline HCV RNA level. CONCLUSIONS: This study shows that a combination therapy of peginterferon and ribavirin is highly effective for chronic HCV infection, producing a high SVR and ETR.

Analysis of Endoscopic Sphincterotomy in Patients with Periampullary Diverticulum: according to the Location of the Diverticulum / 대한소화기내시경학회지

BACKGROUND/AIMS: Endoscopic sphincterotomy (EST) involves more complications and medical problems when a periampullary diverticulum (PD) is present. The data about EST for treating a small population of PD patients is controversial and any recent data is rare. The aim of this study is to evaluate the results of performing EST for a large population of PD patients. METHODS: We retrospectively enrolled 178 patients with PD and 178 patients without PD and these patients underwent EST for removal of common bile duct (CBD) stones during the years 2003~2005 at Dong-A University Hospital. We classified PD patients, according to the location of the ampulla and diverticulum, into 3 groups and we considered removal of the CBD stones as success. RESULTS: The success rates of EST in the two groups were similar: 91.0% in the PD group and 98.8% in the control group (p=0.0341). Failures were more frequently observed when the papilla was located inside of the diverticulum than for the other locations (p=0.0341). The complications cholangitis and pancreatitis after EST were similar for the two groups, but bleeding was more frequently observed in the PD group (p=0.0067). CONCLUSIONS: More skill for performing EST is needed to prevent bleeding in PD patients and it is more difficult to remove CBD stones when the papilla was located inside of the diverticulum.

The Usefulness of the Endoscopic Findings for Predicting Depth of Invasion in Early Gastric Cancer / 대한소화기내시경학회지

BACKGROUND/AIMS: Endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) has been used as a treatment for early gastric cancer (EGC). This study was performed to evaluate the usefulness of the endoscopic findings for diagnosing the depth of invasion in EGC patients. METHODS: We retrospectively analyzed the endoscopic findings of 558 EGC patients who were diagnosed after gastrectomy, EMR or ESD at Dong-A University Hospital between 2000 and 2006, and we divided them into two groups (the mucosa group versus the submucosa group). Nine factors were assessed (Type I or IIa: surface color, surface irregularity, the Yamada type and pitting on the apex; Type IIb: surface color, surface irregularity and marginal definiteness: Type IIc or III: ulcer base irregularity, shape of the converging folds, center of the converging folds and marginal elevation). The tumor size and histologic type were assessed for all the EGCs. RESULTS: Ulcer base irregularity (p=0.005), marginal elevation (p=0.001), and the shape of the converging folds (p=0.018) showed significant correlation with the depth of invasion in type IIc or III EGCs. Tumor size ( <2 cm) showed a significant correlation with mucosal invasion for all the EGCs. CONCLUSIONS: These results support the usefulness of the endoscopic findings for making the therapeutic decision for performing EMR or ESD through predicting the depth of invasion of EGCs.

Rituximab-induced Interstitial Pneumonitis in a Young Patient: A Case Report and Review of the Literature

Side effects of rituximab are mild in most cases, but there have been a few cases of severe pulmonary toxicity reported in elderly patients. Here we report a case of interstitial pneumonitis following rituximab treatment in a young patient. A 35-year-old woman with diffuse large B-cell lymphoma was admitted complaining of dry cough and dyspnea without fever after the 3 treatments with rituximab-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy. Her chest CT with high-resolution CT scanning confirmed the presence of bilateral diffuse ground-glass opacities. The analysis of arterial blood gases indicated hypoxemia. The pulmonary function testing showed a restrictive pattern. There were no other findings suggesting an infection. The findings were compatible with a rituximab-induced interstitial pneumonitis. After the patient was treated with prednisolone, the symptoms resolved. Cases with rituximab-induced interstitial pneumonitis develop principally in elderly patients. However, the condition also can occur in young patients.

Thymosin Alpha-1 in Combination with Pegylated Interferon and Ribavirin in Chronic Hepatitis C Patients Who have Failed to Prior Pegylated Interferon and Ribavirin Treatment

Combination therapy with inteferon-alpha and ribavirin is an approved therapy for patients with chronic hepatitis C. However, even with the use of pegylated interferon, response rates are still poor in many difficult-to-treat groups, especially with genotype 1 and high viral loads. Retreatment of these patients remains challenging. Newer combinations are being investigated to optimize chances of attaining a sustained response in these groups. Thymosin alpha 1 is a polypeptide with immunomodulatory properties that has been suggested to increase response rates in patients with chronic hepatitis C. Herein, we describe two cases of retreatment patients with chronic hepatitis C who have failed prior pegylated interferon and ribavirin therapy. They received triple combination therapies of thymosin alpha 1, pegylated interferon and ribavirin and achieved sustained virological responses. These cases support that thymosin-alpha 1 may increase the efficacy of pegylated interferon plus ribavirin in the treatment of non-responders to previous combination therapy.

Comparisons of the Short-Term Angiographic Outcomes of Cypher and Taxus Stents Implanted in the Same Patient

BACKGROUND AND OBJECTIVES: Drug-eluting stents (DES) have been shown to substantially reduce both angiographic and clinical restenosis. Cypher(R) (sirolimus-eluting stent, Cordis, Johnson and Johnson, Florida, USA) and Taxus(R) (paclitaxel-eluting stent, Boston Scientific, Boston, USA) are the two most widely used DESs, and they both have distinct pharmacological properties and release kinetics. It has been not studied whether these two DESs show different angiographic outcomes when they are simultaneously implanted in the same patient. SUBJECTS AND METHODS: We retrospectively analyzed the angiographic findings of the short-term follow-up in 34 patients (average age: 63 year old, 9 women) in whom both Cypher and Taxus stents were implanted at the same time for the treatment of obstructive coronary lesion. RESULTS: There was no significant difference in the basal angiographic characteristics of the lesions that had two stents deployed in terms of the AHA/ACC classification, reference diameter, the percent diameter stenosis and minimal luminal diameter. The post-procedure results were similar between the two stents. At 6 months follow-up, the Cypher stent displayed significantly less in-stent lumen loss compared with the Taxus stent (0.16+/-0.04 mm vs 0.27+/-0.04 mm; respectively, p=0.040) and a smaller percent diameter stenosis (15.9+/-1.3% vs 19.9+/-2.2%, respectively, p=0.049). CONCLUSION: The Cypher stent showed significantly less luminal loss during short term follow-up compared with the Taxus stent when implanted in the same patient. This result suggests that in a given individual patient, the Cypher stent induces less neointimal proliferation than does the Taxus stent.