Little is known about the prevalence of mucosal antibodies induced by infection with human coronaviruses (HCoV), including HCoV-229E and -OC43 and recently described strains (HCoV-NL63 and -HKU1). By enzyme-linked immunosorbent assay, we measured anti-HCoV IgG antibodies in serum and IgA antibodies in nasal wash specimens collected at seven U.S. sites from 105 adults aged 50 years and older (mean age, 67 ؎ 9 years) with chronic obstructive pulmonary disease. Coronaviruses comprise a genus of the family Coronaviridae and are enveloped, single-stranded, positive-sense RNA viruses (30). Four human coronavirus (HCoV) strains have been described, which are associated with a spectrum of disease, from mild, febrile upper respiratory tract illnesses to severe illnesses, including croup, bronchiolitis, and pneumonia, and have a wide geographic distribution (1, 2, 6, 7, 9-14, 16, 20, 25, 26, 31, 32, 35, 39-46). HCoV infection has been a contributor to severe illnesses requiring emergency care and hospitalization of patients with chronic medical conditions (7,9,12,15,16,21,22).The earliest-described HCoV strains, HCoV-229E and HCoV-OC43, which are group I and group II coronaviruses, respectively, have now been joined by the more recently described group I and II strains HCoV-NL63 and HCoV-HKU1 (13,30,42,45,46), which were discovered in the search for other pathogenic coronaviruses after the identification of the coronavirus that causes severe acute respiratory syndrome (SARS) (29). HCoV-NL63 may have infected human populations for a long time, since it diverged phylogenetically from HCoV-229E about 1,000 years ago (33), and seroprevalence would likely be high as a result. Cross-sectional and longitudinal seroepidemiological studies have found large proportions of children and healthy adults to have detectable serum antibodies to the four HCoV strains, and seroconversion occurs often in childhood; seroprevalence increases with age, and reinfections may occur (5,8,23,28,(36)(37)(38). More information is needed about the seroprevalence of these viruses, the durability of the humoral immune response, correlates of immunity, and mucosal antibody responses to HCoV infection. The present study questioned whether the prevalence of antibodies to the four HCoV strains would be different in nasal secretions than in serum of older adult veterans with underlying chronic obstructive pulmonary disease (COPD) who participated in Department of Veterans Affairs Cooperative Study 448 (18). MATERIALS AND METHODSSubjects. A convenience sample of 105 patients who met spirometric criteria for COPD and were enrolled in a larger influenza virus vaccine efficacy trial of patients Ն50 years of age (18) were chosen for analysis in this substudy of the prevalence of antibodies to HCoV, because residual serum and nasal wash specimens collected at the same time for each subject were available for analysis. The 105 subjects were enrolled at seven geographically diverse study sites in the United States, located in the following states: Alabama, Florida,...
Human coronaviruses (HCoV) are common causes of respiratory illnesses (RI) despite preexisting humoral immunity. Sera were obtained near the onset of RI and 3 to 4 weeks later as part of a prospective study of 200 subjects evaluated for RI from 2009 to 2013. Antibodies against common HCoV strains were measured by enzyme-linked immunosorbent assay and neutralization assay comparing older adults with cardiopulmonary diseases (99 subjects) to younger, healthy adults (101 subjects). Virus shedding was detected in respiratory secretions by polymerase chain reaction. Of 43HCoV-associated illnesses, 15 (35%) occurred in 14 older adults (aged ≥60 years) and 28 (65%) in 28 younger adults (aged 21-40 years). Binding and neutralizing antibodies were higher in older adults. Only 16 (35.7%) of RI with increases in binding antibodies also had increases in neutralizing antibodies to HCoV. Increases in binding antibodies with RI were more frequent than increased neutralizing antibodies and virus shedding, and more frequent in younger compared to older adults. Functional neutralizing antibodies were not stimulated as often as binding antibodies, explaining in part a susceptibility to reinfection with HCoV. Monitoring binding antibodies may be more sensitive for the serologic detection of HCoV infections. K E Y W O R D Santibody, coronavirus, immunity, neutralization, respiratory illness
Bortezomib (Velcade, formerly PS-341) is proteasome inhibitor with documented antitumor activity in multiple myeloma and other lymphoid malignancies. We performed a Phase I study to investigate the maximum tolerated dose and dose-limiting toxicity of bortezomib in patients with acute leukemias refractory to or relapsing after prior therapy. Fifteen patients were treated with 0.75 (n ؍ 3), 1.25 (n ؍ 7), or 1.5 (n ؍ 5) mg/m 2 bortezomib administered twice weekly for 4 weeks every 6 weeks. Dose-limiting toxicity included orthostatic hypotension (n ؍ 2), nausea (n ؍ 2), diarrhea (n ؍ 1), and fluid retention (n ؍ 1), all at 1.5 mg/m 2 bortezomib. Proteasome inhibition was dose dependent and reached 68% at 1.5 mg/m 2 bortezomib. Peak inhibition was observed 1 h after treatment and returned to near baseline levels by 72 h after treatment. Incubation of blast cells with bortezomib in vitro showed induction of apoptosis in three of five patients investigated. We conclude that the maximum tolerated dose of bortezomib in patients with acute leukemia is 1.25 mg/m 2 , using a twice-weekly for 4 weeks every 6 weeks schedule. The in vitro evidence of antileukemia and transient hematological improvements observed in some patients warrants further investigation of bortezomib in acute leukemias, probably in combination with other agents.
Respiratory illnesses were commonly associated with coronaviruses and enteroviruses/rhinoviruses affecting chronically ill, older patients more than healthy, young adults.
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