Distinguishing Incubation and Acute Disease Stages of Mild-to-Moderate COVID-19

While numerous studies have already compared the immune responses against SARS-CoV-2 in severely and mild-to-moderately ill COVID-19 patients, longitudinal trajectories are still scarce. We therefore set out to analyze serial blood samples from mild-to-moderately ill patients in order to define the immune landscapes for differently progressed disease stages. Twenty-two COVID-19 patients were subjected to consecutive venipuncture within seven days after diagnosis or admittance to hospital. Flow cytometry was performed to analyze peripheral blood immune cell compositions and their activation as were plasma levels of cytokines and SARS-CoV-2 specific immunoglobulins. Healthy donors served as controls. Integrating the kinetics of plasmablasts and SARS-CoV-2 specific antibodies allowed for the definition of three disease stages of early COVID-19. The incubation phase was characterized by a sharp increase in pro-inflammatory monocytes and terminally differentiated cytotoxic T cells. The latter correlated significantly with elevated concentrations of IP-10. Early acute infection featured a peak in PD-1⁺ cytotoxic T cells, plasmablasts and increasing titers of virus specific antibodies. During late acute infection, immature neutrophils were enriched, whereas all other parameters returned to baseline. Our findings will help to define landmarks that are indispensable for the refinement of new anti-viral and anti-inflammatory therapeutics, and may also inform clinicians to optimize treatment and prevent fatal outcomes.     

Whom to treat? The contribution of vertebral X-rays to risk-based algorithms for fracture prediction. Results from the European Prospective Osteoporosis Study

Introduction Vertebral fracture is a strong risk factor for future spine and hip fractures; yet recent data suggest that only 5–20% of subjects with a spine fracture are identified in primary care. We aimed to develop easily applicable algorithms predicting a high risk of future spine fracture in men and women over 50 years of age.Methods Data was analysed from 5,561 men and women aged 50+ years participating in the European Prospective Osteoporosis Study (EPOS). Lateral thoracic and lumbar spine radiographs were taken at baseline and at an average of 3.8 years later. These were evaluated by an experienced radiologist. The risk of a new (incident) vertebral fracture was modelled as a function of age, number of prevalent vertebral fractures, height loss, sex and other fracture history reported by the subject, including limb fractures occurring between X-rays. Receiver Operating Characteristic (ROC) curves were used to compare the predictive ability of models.Results In a negative binomial regression model without baseline X-ray data, the risk of incident vertebral fracture significantly increased with age [RR 1.74, 95% CI (1.44, 2.10) per decade], height loss [1.08 (1.04, 1.12) per cm decrease], female sex [1.48 (1.05, 2.09)], and recalled fracture history; [1.65 (1.15, 2.38) to 3.03 (1.66, 5.54)] according to fracture site. Baseline radiological assessment of prevalent vertebral fracture significantly improved the areas subtended by ROC curves from 0.71 (0.67, 0.74) to 0.74 (0.70, 0.77) P=0.013 for predicting 1+ incident fracture; and from 0.74 (0.67, 0.81) to 0.83 (0.76, 0.90) P=0.001 for 2+ incident fractures. Age, sex and height loss remained independently predictive. The relative risk of a new vertebral fracture increased with the number of prevalent vertebral fractures present from 3.08 (2.10, 4.52) for 1 fracture to 9.36 (5.72, 15.32) for 3+. At a specificity of 90%, the model including X-ray data improved the sensitivity for predicting 2+ and 1+ incident fractures by 6 and 4 fold respectively compared with random guessing. At 75% specificity the improvements were 3.2 and 2.4 fold respectively. With the modelling restricted to the subjects who had BMD measurements (n=2,409), the AUC for predicting 1+ vs. 0 incident vertebral fractures improved from 0.72 (0.66, 0.79) to 0.76 (0.71, 0.82) upon adding femoral neck BMD (P=0.010).Conclusion We conclude that for those with existing vertebral fractures, an accurately read spine X-ray will form a central component in future algorithms for targeting treatment, especially to the most vulnerable. The sensitivity of this approach to identifying vertebral fracture cases requiring anti-osteoporosis treatment, even when X-rays are ordered highly selectively, exceeds by a large margin the current standard of practice as recorded anywhere in the world.This work was presented in part at the 30th European Symposium on Calcified Tissues, 8–12 May 2003, Rome, Italy.A.J. Silman and J. Reeve are the EU Grant holders and Project Leaders.     

Preoperative radiation therapy in clinical stage II endometrial carcinoma.

From 1980 to 1987, 30 patients with FIGO clinical Stage II carcinoma of the endometrium were treated with 5000 cGy preoperative pelvic radiation therapy at Thomas Jefferson University Hospital. Patients with gross cervical disease received additional intracavitary irradiation with a tandem and ovoids for a combined total dose of 7000 cGy to point A. All patients then underwent exploratory laparotomy, total abdominal hysterectomy, and bilateral salpingo-oophorectomy (TAH/BSO). The 5-year actuarial survival for the entire group was 69%. The 5-year actuarial survival for the 8 patients with papillary serous, clear cell, and undifferentiated small cell carcinoma was 38%, with most patients failing in the upper abdomen. The 5-year actuarial survival for the remaining 22 patients was 82%. The only local failure occurred in the patient with an undifferentiated small cell carcinoma. Although preoperative pelvic radiation therapy together with TAH/BSO appears to offer excellent local control in all patients with Stage II endometrial carcinoma, additional treatment options should be considered for patients with papillary serous and clear cell histologies because of the poor survival and high failure rate in the upper abdomen.     

Mortality and morbidity of newborn infants in intensive care (birth weight less than 1,501 grams)

A comparative analysis of the mortality and morbidity of premature infants with a birthweight below 1.501 g, born in the years 1974, 1978 and 1981, is given. The mortality rate has remained unchanged in the years 1974 (when a neonatal intensive care unit was installed at the University Children's Hospital Graz) and 1981 with 33% and 32% respectively. The total number of admissions rose from 36 (1974) to 67 (1978) and 91 (1981). Simultaneously the number of patients, who needed neonatal intensive care increased. Whilst in 1974 only 2 of 24 surviving infants needed artificial ventilation, in 1978 19 of 38 patients had respirator therapy. Despite the increasing severity of neonatal affections the number of severe handicaps caused by perinatal complications remained constantly low with altogether 5 cases in the years 1978 and 1981. Two children had a spastic tetraplegia, two others had a posthaemorrhagic hydrocephalus and one child was blind due to bilateral septic abscesses of the vitreous body. Only two of these children had long time artificial ventilation. Approximately 80% of the surviving children exhibited normal psychomotor development and showed no neurological sequelae. This rate was unchanged in the investigated periods.     

PPD-induced monocyte chemotactic factor production by human milk cells

The functional capability of antigen-stimulated breast milk cells to produce an immunologic mediator was examined. Colostrum and comparison peripheral blood samples were obtained from ten women, two to four days postpartum, and supernatants from PPD-stimulated mononuclear cell cultures were assayed for the lymphokine, monocyte chemotactic factor. Five of the ten women studied had a history of a positive tuberculin skin test and one had received BCG immunization. Peripheral blood lymphocyte cultures and colostrum cell cultures from four of these six women produced monocyte chemotactic factor. These results demonstrated the functional capability of antigen-stimulated colostral cells to produce immunologic mediators.     

A heroin epidemic at the intersection of histories: the 1960s epidemic among African Americans in Baltimore

In the drug field the fundamental epidemiological question-why illicit drug use, here, now, among these people-has still not been adequately answered. Drawing on the work of colleagues in medical anthropology, we attempt to move closer to an answer by developing a "trend theory." In this article we analyze a single case: the increase in heroin use and addiction among African Americans in the City of Baltimore in the 1960s. We found that the two most important historical processes behind the epidemic were (1) a changing distribution/supply system and (2) the mix of hope and despair that was part of the early civil rights movement.     

Safety and immunogenicity of acellular pertussis vaccine combined with diphtheria and tetanus toxoids in 17- to 24-month-old children.

A double-blind, randomized, controlled trial comparing 4 lots of acellular pertussis-diphtheria tetanus toxoids vaccine (APDT) to whole cell DTP vaccine in 397 children was conducted at 7 clinical centers. Children were immunized at 17 to 24 months of age and sera were obtained pre- and postimmunization. Sera were analyzed for antibody to pertussis antigens (pertussis toxin, filamentous hemagglutinin, with a molecular weight of 69,000 (69k) outer membrane protein and agglutinogens) and to diphtheria and tetanus toxoids. Information concerning local reactions and systemic events was collected daily for 10 days postimmunization. The acellular vaccine produced significantly fewer local reactions than whole cell DTP. Parents reported that drowsiness or fretfulness occurred significantly less often in APDT vaccine recipients compared with whole cell DTP recipients. Fever greater than or equal to 38.3 degrees C occurred in 8% of APDT vaccine recipients and in 15% of whole cell DTP vaccine recipients (P = 0.06). The only significant difference in immune response to pertussis antigens between the two vaccines was for filamentous hemagglutinin (P less than 0.01) for which significantly higher antibody concentrations were found in the APDT vaccine group. We conclude that this APDT vaccine is safe and immunogenic when administered as a booster dose to 18-month-old children.