Shared B cell memory to coronaviruses and other pathogens varies in human age groups and tissues

Vaccination and infection promote the formation, tissue distribution, and clonal evolution of B cells encoding humoral immune memory. We evaluated convergent antigen-specific antibody genes of similar sequences shared between individuals in pediatric and adult blood, and deceased organ donor tissues. B cell memory varied for different pathogens. Polysaccharide antigen-specific clones were not exclusive to the spleen. Adults convergent clones often express mutated IgM or IgD in blood and are class-switched in lymphoid tissues; in contrast, children have abundant class-switched convergent clones in blood. Consistent with serological reports, pre-pandemic children had class-switched convergent clones to SARS-CoV-2, enriched in cross-reactive clones for seasonal coronaviruses, while adults showed few such clones in blood or lymphoid tissues. These results extend age-related and anatomical mapping of human humoral pathogen-specific immunity. One Sentence SummaryChildren have elevated frequencies of pathogen-specific class-switched memory B cells, including SARS-CoV-2-binding clones.

Reinfection with SARS-CoV-2 and Failure of Humoral Immunity: a case report.

Recovery from COVID-19 is associated with production of anti-SARS-CoV-2 antibodies, but it is uncertain whether these confer immunity. We describe viral RNA shedding duration in hospitalized patients and identify patients with recurrent shedding. We sequenced viruses from two distinct episodes of symptomatic COVID-19 separated by 144 days in a single patient, to conclusively describe reinfection with a new strain harboring the spike variant D614G. With antibody and B cell analytics, we show correlates of adaptive immunity, including a differential response to D614G. Finally, we discuss implications for vaccine programs and begin to define benchmarks for protection against reinfection from SARS-CoV-2.

Human B cell clonal expansion and convergent antibody responses to SARS-CoV-2

During virus infection B cells are critical for the production of antibodies and protective immunity. Here we show that the human B cell compartment in patients with diagnostically confirmed SARS-CoV-2 and clinical COVID-19 is rapidly altered with the early recruitment of B cells expressing a limited subset of IGHV genes, progressing to a highly polyclonal response of B cells with broader IGHV gene usage and extensive class switching to IgG and IgA subclasses with limited somatic hypermutation in the initial weeks of infection. We identify extensive convergence of antibody sequences across SARS-CoV-2 patients, highlighting stereotyped naive responses to this virus. Notably, sequence-based detection in COVID-19 patients of convergent B cell clonotypes previously reported in SARS-CoV infection predicts the presence of SARS-CoV/SARS-CoV-2 cross-reactive antibody titers specific for the receptor-binding domain. These findings offer molecular insights into shared features of human B cell responses to SARS-CoV-2 and other zoonotic spillover coronaviruses.

Prognostic Significance of Initial Platelet Counts and Fibrinogen Level in Advanced Non-Small Cell Lung Cancer

Thrombocytosis and coagulation systems activation are commonly associated with disease progression and are suggested poor prognostic factors in patients with malignancies. This study aimed to investigate the prevalence and prognostic significance of thrombocytosis and elevated fibrinogen levels in patients with advanced non-small cell lung cancer (NSCLC). Initial platelet counts and fibrinogen levels were reviewed in 854 patients with histologically proven NSCLC. Thrombocytosis was defined as platelet counts > 450 x 10(9)/L. A serum fibrinogen level > 4.5 g/L was considered high. At the time of diagnosis, initial platelet counts and serum fibrinogen levels were evaluated before treatment. Clinicopathologic data including histological type, tumor, node, metastasis (TNM) stage, performance status, treatment method, and survival time were evaluated. Initial thrombocytosis was found in 6.9% of patients, and elevated fibrinogen levels were found in 55.1% of patients. Patients with thrombocytosis had a significantly poorer prognosis than patients with normal platelet counts (P < 0.001). In multivariate survival analysis, thrombocytosis was an independent prognostic factor (P < 0.001). An elevated serum fibrinogen level was associated with poor prognosis (P < 0.001). In conclusion, initial thrombocytosis and a high fibrinogen level are independent factors for predicting poor prognosis in patients with advanced NSCLC.

The Efficacy of Ultrasonography in Identifying Fracture Patterns of Nasal Bone

PURPOSE: The purpose of this study was to know whether ultrasonography is proper diagnostic tool for decision of treatment method or not, as compared the efficacy of US in allowing identifying fracture patterns of nasal bone with that of CT. MATERIALS AND METHODS: Fifty patients with nasal trauma were investigated prospectively by CT and US. According to CT and ultrasonographic findings, each case of nasal bone injury were rated as grade 1 (nasal injury but not fracture), grade 2 (simple fracture without displacement), grade 3 (unilateral simple fracture with displacement), grade 4 (bilateral simple fractures with displacement), and grade 5 (bilateral comminuted fractures with depression). Assessment for ultrasonographic method were defined as overestimations or underestimation according to whether the nasal fracture had been assigned a higher or lower grade at the review of the findings of CT. The correlation between the results of CT and ultrasonography were measured. RESULTS: In ultrasonographic estimation of grade of 50 cases of nasal bone injuries, there were correctly graded in 42 cases, overestimated in 5 cases, underestimated in 3 cases. In allowing accurate grading of nasal bone injury, images of nasal ultrasonography correlated closely with those of CT (r = 0.796). CONCLUSION: Nasal ultrasonography is a reliable method that allows appropriate grading of nasal bone injury and would be a useful first line imaging method in providing the detail necessary for proper management of patients with mild simple nasal bone injury.

A Case of Fibrous Hamartoma of Infancy with Hypertrichosis on the Axilla / 대한피부과학회지

Fibrous hamartoma of infancy is a rare benign lesion that presents as a solitary, painless, flesh-colored, subcutaneous mass. Most of these lesions occur in the axillary region, the upper arm, the upper trunk, the inguinal area and the external genital area. The lesion histologically consists of three different components in varying proportions: well-defined fibrous trabeculae, primitive mesenchyme and, mature adipose tissue. Overlying skin changes are uncommon, including alternations in pigmentation, eccrine gland hyperplasia and increased hair. To the best of our knowledge, only 6 cases of fibrous hamartoma of infancy with hypertrichosis have been reported. In these six cases, the lesions were located on the buttocks and back, which were non-predilection sites. We report the first case of fibrous hamartoma of infancy with hypertrichosis on the axilla, which is known as a predilection site.