ResearchPad - brief-reports https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[An Inflammatory Profile Correlates With Decreased Frequency of Cytotoxic Cells in Coronavirus Disease 2019]]> https://www.researchpad.co/article/elastic_article_12427 Increased production of inflammatory cytokines and myeloid-derived suppressor cells occurs in patients with coronavirus disease 2019. These inversely correlated with perforin-expressing natural killer (NK) and CD3+ T cells. We observed a lower number of perforin-expressing NK cells in intensive care unit (ICU) patients compared with non-ICU patients, suggesting an impairment of the immune cytotoxic arm as a pathogenic mechanism.

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<![CDATA[Common Adverse Events Associated with the Use of Ribavirin for Severe Acute Respiratory Syndrome in Canada]]> https://www.researchpad.co/article/elastic_article_11686 Although information on efficacy and adverse drug reactions is lacking, ribavirin has been used empirically for the treatment of severe acute respiratory syndrome (SARS). We report common adverse events in 110 patients with suspected or probable SARS who were treated with ribavirin. Sixty-one percent of the patients had evidence of hemolytic anemia, and hypocalcemia and hypomagnesmia were reported in 58% and 46% of patients, respectively.

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<![CDATA[Human Bocavirus Infection in Young Children in the United States: Molecular Epidemiological Profile and Clinical Characteristics of a Newly Emerging Respiratory Virus<a href="#fn1"/>]]> https://www.researchpad.co/article/elastic_article_11679 BackgroundHuman bocavirus (HBoV) is a newly identified human parvovirus that was originally identified in the respiratory secretions of children with respiratory tract disease. To further investigate the epidemiological profile and clinical characteristics of HBoV infection, we screened infants and children <2 years of age (hereafter referred to as “children”) for HBoV

MethodsChildren for whom respiratory specimens submitted to a diagnostic laboratory tested negative for respiratory syncytial virus, parainfluenza viruses (types 1–3), influenza A and B viruses, and adenovirus, as well as asymptomatic children, underwent screening for HBoV by use of polymerase chain reaction (PCR). Respiratory specimens were obtained from the children from 1 January 2004 through 31 December 2004

ResultsTwenty-two (5.2%) of the 425 children who had a respiratory specimen submitted to the diagnostic laboratory and 0 of the 96 asymptomatic children were found to be positive for HBoV by PCR (P=.02). Fever, rhinorrhea, cough, and wheezing were observed in ⩾50% of the HBoV-positive children. Of the 17 children who had chest radiography performed, 12 (70.6%) had abnormal findings. HBoV appeared to have a seasonal distribution. Nucleotide polymorphisms were detected in the viral capsid protein (VP) 1/VP2 genes. Two distinct HBoV genotypes circulated during the study period

ConclusionsHBoV is circulating in the United States and is associated with both upper and lower respiratory tract disease in infants and young children

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<![CDATA[Open Reading Frame 8a of the Human Severe Acute Respiratory Syndrome Coronavirus Not Only Promotes Viral Replication but Also Induces Apoptosis]]> https://www.researchpad.co/article/elastic_article_11676 Background. A unique genomic difference between human and civet severe acute respiratory syndrome coronaviruses (SARS-CoVs) is that the former has a deletion of 29 nucleotides from open reading frame (orf) 8d that results in the generation of orf8a and orf8b. The objectives of the present study were to analyze antibody reactivity to ORF8a in patients with SARS and to elucidate the function of ORF8a.

Methods. Western-blot and immunofluorescent antibody assays were used to detect anti-ORF8a antibody. SARS-CoV HKU39849 was used to infect stable clones expressing ORF8a and cells transfected with small interfering RNA (siRNA). The virus loads (VLs) and cytopathic effects (CPEs) were recorded. Confocal microscopy and several mitochondria-related tests were used to study the function of ORF8a.

Results. Two (5.4%) of 37 patients with SARS had anti-ORF8a antibodies. The VLs in the stable clones expressing ORF8a were significantly higher than those in control subjects 5 days after infection. siRNA against orf8a significantly reduced VLs and interrupted the CPE. ORF8a was found to be localized in mitochondria, and overexpression resulted in increases in mitochondrial transmembrane potential, reactive oxygen species production, caspase 3 activity, and cellular apoptosis.

Conclusions. ORF8a not only enhances viral replication but also induces apoptosis through a mitochondria-dependent pathway.

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<![CDATA[Fixed Dosing of Liposomal Amphotericin B in Morbidly Obese Individuals]]> https://www.researchpad.co/article/elastic_article_10881 In this prospective study, we examined the pharmacokinetics of 1 and 2 mg/kg liposomal amphotericin B in 16 morbidly obese individuals (104–177 kg). Body size had no effect on clearance. We recommend a fixed dose in patients ≥100 kg (ie, 300 or 500 mg rather than the current dose of 3 and 5 mg/kg, respectively).

Clinical Trials Registration NCT02320604.

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<![CDATA[ <i>Chlamydia trachomatis</i> Infection of the Neovagina in Transgender Women]]> https://www.researchpad.co/article/Ne4b682ec-64bd-4209-8e3a-cf7d14bf8281 We report 2 cases of neovaginal Chlamydia trachomatis infection in transgender women who underwent penile-inversion vaginoplasty procedures with integrated peritoneum and urethral grafts. These tissue types may have facilitated C. trachomatis infection. Medical providers should implement neovaginal screening for bacterial sexually transmitted infections in transgender patients at risk for infection.

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<![CDATA[Molecular Epidemiology of Severe Acute Respiratory Syndrome–Associated Coronavirus Infections in Taiwan<a href="#fn1"/>]]> https://www.researchpad.co/article/N8d1f2f8f-e475-40c8-9099-113397b69b45 Background In 2003, Taiwan experienced a series of outbreaks of severe acute respiratory syndrome (SARS) and 1 laboratory-contamination accident. Here we describe a new phylogenetic analytical method to study the sources and dissemination paths of SARS-associated coronavirus (SARS-CoV) infections in Taiwan

Methods A phylogenetic analytical tool for combining nucleotide sequences from 6 variable regions of a SARS-CoV genome was developed by use of 20 published SARS-CoV sequences; and this method was validated by use of 80 published SARS-CoV sequences. Subsequently, this new tool was applied to provide a better understanding of the entire complement of Taiwanese SARS-CoV isolates, including 20 previously published and 19 identified in this study. The epidemiological data were integrated with the results from the phylogenetic tree and from the nucleotide-signature pattern

Results The topologies of phylogenetic trees generated by the new and the conventional strategies were similar, with the former having better robustness than the latter, especially in comparison with the maximum-likelihood trees: the new strategy revealed that during 2003 there were 5 waves of epidemic SARS-CoV infection, which belonged to 3 phylogenetic clusters in Taiwan

Conclusions The new strategy is more efficient than its conventional counterparts. The outbreaks of SARS in Taiwan originated from multiple sources

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<![CDATA[Safety and Immunogenicity of the Respiratory Syncytial Virus Vaccine RSV/ΔNS2/Δ1313/I1314L in RSV-Seronegative Children]]> https://www.researchpad.co/article/N995bb3e9-b66b-4e90-a450-bd56d19e3756 A live attenuated respiratory syncytial virus (RSV) vaccine containing a deletion of the interferon antagonist NS2 gene and mutations in the polymerase gene was well tolerated and infectious, inducing primary neutralizing antibody responses and potent memory antibody responses in RSV-seronegative children.

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<![CDATA[Neutralizing Antibodies in Patients with Severe Acute Respiratory Syndrome-Associated Coronavirus Infection]]> https://www.researchpad.co/article/N3dcab851-017a-48da-b441-5cd966e28aee Background. Severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) is the principal etiologic agent of SARS. We analyzed serum samples obtained from 623 patients with SARS in Beijing, to determine whether infection with SARS-CoV can elicit neutralizing antibodies (NAbs).

Methods. We developed a highly sensitive and safe neutralization assay using the SARS-CoV pseudotyped virus and used this assay to determine the titers of the NAbs in serum samples from patients with SARS.

Results. We found that 85.9% of serum samples contained NAbs against SARS-CoV and that most of the NAb activities could be attributed to immunoglobulin G. The NAbs became detectable first at 5–10 days after the onset of symptoms, and their levels peaked at 20–30 days and then were sustained for >150 days. The serum samples could neutralize the pseudotype particles bearing the spike glycoproteins from different SARS-CoV strains, suggesting that the NAbs to SARS-CoV were broadly reactive.

Conclusions. NAbs to SARS-CoV are broadly elicited in patients with SARS and, according to their kinetics, may correlate with viral load during the early stages of the disease. These results suggest that it is possible to develop effective vaccines against SARS and that NAbs provide a potential strategy for treating patients with SARS.

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<![CDATA[Association between a Novel Human Coronavirus and Kawasaki Disease]]> https://www.researchpad.co/article/Nd6a74fa8-0d4e-4bfa-95e3-759c75b05115 Kawasaki disease is a systemic vasculitis of childhood; its etiology is unknown. We identified evidence of a novel human coronavirus, designated “New Haven coronavirus” (HCoVNH), in respiratory secretions from a 6-month-old infant with classic Kawasaki disease. To further investigate the possible association between HCoV-NH infection and Kawasaki disease, we conducted a case-control study. Specimens of respiratory secretions from 8 (72.7%) of 11 children with Kawasaki disease and from 1 (4.5%) of 22 control subjects (children without Kawasaki disease matched by age and the time the specimens were obtained) tested positive for HCoVNH by reverse-transcriptase polymerase chain reaction (Mantel-Haenszel matched odds ratio, 16.0 [95% confidence interval, 3.4–74.4]; P = .0015). These data suggest that HCoV-NH infection is associated with Kawasaki disease.

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<![CDATA[Contact Tracing for COVID-19: An Opportunity to Reduce Health Disparities and End the Human Immunodeficiency Virus/AIDS Epidemic in the United States]]> https://www.researchpad.co/article/Nd85727cc-ff2e-46b0-aa42-c7909919c38e Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing and contact tracing have been proposed as critical components of a safe and effective coronavirus disease 2019 (COVID-19) public health strategy. We argue that COVID-19 contact tracing may provide a unique opportunity to also conduct widespread HIV testing, among other health-promotion activities.

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<![CDATA[Interferon-Induced Transmembrane Protein 3 Genetic Variant rs12252-C Associated With Disease Severity in Coronavirus Disease 2019]]> https://www.researchpad.co/article/Nbca07851-1b8c-4468-915b-517516aaf38c We report evidence of an age-dependent allelic association between interferon-induced transmembrane protein 3 (rs12252 allele) and severity of coronavirus disease 2019, highlighting the need for further studies and the potential for a personalized, genotype-based approach to identifying high-risk individuals.

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<![CDATA[US College Students Are at Increased Risk for Serogroup B Meningococcal Disease]]> https://www.researchpad.co/article/N0ac3d2f3-0af3-400b-ae79-58db749e57f5 Publicly available surveillance data, Centers for Disease Control and Prevention reports, and other sources suggest that college students in the United States are at increased risk for meningococcus serogroup B (MenB) disease.

US surveillance data from 2015 to 2017 show that the incidence of invasive meningococcal disease (IMD) was greater among college students than among those not attending college; the average annual incidence of MenB disease was >5-fold higher among college students, and all college IMD outbreaks between 2011 and March 2019 were caused by MenB.

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<![CDATA[Multiple organ failure and coma as initial presentation of pheochromocytoma in a patient with multiple endocrine neoplasia (MEN) type II A]]> https://www.researchpad.co/article/N253bd136-f396-4acf-ad1a-bf61b30bd1bf

The unusual case of a 65-year-old woman with intermittent hypotension, fever, pulmonary edema and coma as initial presentation of pheochromocytoma is reported. The patient developed respiratory, cardiac and renal failure, disseminated intravascular coagulation and liver dysfunction. She, had to be defibrillated on multiple occasions, occurring in periods of severe hypertension. After successful surgical removal of a pheochromocytoma a thyroid medullary carcinoma was detected. Several members of the patients family had presented with multiple endocrine neoplasia (MEN II).

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<![CDATA[High-Altitude Hypoxia Decreases Plasma Erythropoietin Soluble Receptor Concentration in Lowlanders]]> https://www.researchpad.co/article/N651edca9-77f7-40ae-b3b0-dba39d785973

Background: The soluble form of the erythropoietin (Epo) receptor (sEpoR) is an endogenous antagonist of Epo. Decreasing plasma sEpoR increases free Epo, thereby increasing the availability of the hormone. In humans, short-term intermittent normobaric hypoxia exposure reduces sEpoR concentration in plasma. However, whether similar changes occur during continuous hypoxia, such as during high-altitude exposure with ongoing acclimatization, is yet unknown. Therefore, this study aimed to characterize the time-course concentration profile of sEpoR, and also of Epo, reticulocyte count (RC), and hematocrit in healthy lowlanders during 4 days at high altitude.

Methods: Twenty-two men residents at sea level traveled by road (∼7 hours) from Lima to Cerro de Pasco (4340 m) for 72 hours. Oxygen saturation as measured by pulse oximetry (SpO2), heart rate, systolic and diastolic blood pressure, Lake Louise Score, sEpoR, Epo, RC, and hematocrit were evaluated every 12 hours, starting 12 hours before the ascent.

Results: Plasma sEpoR decreased by 19% and remained below baseline values throughout high-altitude exposure. In parallel, Epo levels increased during the first hours, reaching a peak at 48 hours, and then progressively decreased until 72 hours. As a result, the Epo-to-sEpoR ratio (Epo/sEpoR) remained significantly elevated compared with baseline values. RC increased linearly until the end of the protocol, and hematocrit only showed a marginal increase.

Conclusion: Our results show that high-altitude hypoxia causes a significant and stable reduction of plasma sEpoR concentration within the first 24 hours, whereas plasma Epo constantly decreases after having reached a maximum by 48 hours. This simultaneous change leads to a relatively high Epo/sEpoR after 72 hours at high altitude. The early increase in hematocrit likely relates to hemoconcentration, but the steady increase in RC reflects a sustained erythropoietic drive that will lead to elevate hematocrit to a new steady state after acclimatization.

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<![CDATA[Blinded Case‐Control Study of the Relationship between Human Coronavirus NL63 and Kawasaki Syndrome]]> https://www.researchpad.co/article/N84c0cc85-b665-4ff7-848e-7448fb421428

Abstract

We conducted a blinded, case‐control, retrospective study in pediatric patients hospitalized at The Children’s Hospital, Denver, Colorado, to determine whether human coronavirus (HCoV)–NL63 infection is associated with Kawasaki syndrome (KS). Over the course of a 7‐month period, nasopharyngeal‐wash samples from 2 (7.7%) of 26 consecutive children with KS and 4 (7.7%) of 52 matched control subjects tested positive for HCoV‐NL63 by reverse transcription–polymerase chain reaction. These data suggest that, although HCoV‐NL63 was circulating in children in our community during the time of the study, the prevalence of infection with HCoV‐NL63 was not greater in patients with KS than in control subjects.

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<![CDATA[Exceptionally Potent Cross-Reactive Neutralization of Nipah and Hendra Viruses by a Human Monoclonal Antibody]]> https://www.researchpad.co/article/N523c03a1-e788-40fd-8304-2d7f68dca285

Abstract

We have previously identified neutralizing human monoclonal antibodies against Nipah virus (NiV) and Hendra virus (HeV) by panning a large nonimmune antibody library against a soluble form of the HeV attachment-envelope glycoprotein G (sGHeV). One of these antibodies, m102, which exhibited the highest level of cross-reactive neutralization of both NiV and HeV G, was affinity maturated by light-chain shuffling combined with random mutagenesis of its heavy-chain variable domain and panning against sGHeV. One of the selected antibody Fab clones, m102.4, had affinity of binding to sGHeV that was equal to or higher than that of the other Fabs; it was converted to IgG1 and tested against infectious NiV and HeV. It exhibited exceptionally potent and cross-reactive inhibitory activity with 50% inhibitory concentrations below 0.04 and 0.6 μg/mL, respectively. The virus-neutralizing activity correlated with the binding affinity of the antibody to sGHeV and sGNiV. m102.4 bound a soluble form of NiV G (sGNiV) better than it bound sGHeV, and it neutralized NiV better than HeV, despite being originally selected against sGHeV. These results suggest that m102.4 has potential as a therapeutic agent for the treatment of diseases caused by henipaviruses. It could be also used for prophylaxis and diagnosis, and as a research reagent

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<![CDATA[Spectrum of Viruses and Atypical Bacteria in Intercontinental Air Travelers with Symptoms of Acute Respiratory Infection]]> https://www.researchpad.co/article/N27630fbe-f31d-4772-b939-73dd4c583479

Abstract

Respiratory infections after air travel are frequent, but epidemiological data are incomplete. Using sensitive polymerase chain reactions, we studied the spectrum of atypical bacteria and respiratory viruses in travelers fulfilling the case definition of severe acute respiratory syndrome. A pathogen was identified in 67 travelers (43.2%). Influenza and parainfluenza viruses were most prevalent, at 14.2% and 15.5%, respectively. Prevalences of adenoviruses, human metapneumovirus, coronaviruses, and rhinoviruses ranged between 2.6% and 4.8%. Human bocavirus, respiratory syncytial virus, and Legionella, Mycoplasma, and Chlamydophila species were absent or appeared at frequencies of <1%. To our knowledge, these are the first specific baseline data for the mentioned agents in the context of air travel.

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<![CDATA[Epidemiological Profile and Clinical Associations of Human Bocavirus and Other Human Parvoviruses]]> https://www.researchpad.co/article/N9768861c-63c2-43ad-add6-6bd4efc9372d

Abstract

BackgroundHuman bocavirus (HBoV) and PARV4 are newly discovered human parvoviruses. HBoV, which was first detected in respiratory samples, has a potential role in the development of human respiratory disease. The present study compared the frequencies, epidemiological profiles, and clinical backgrounds of HBoV and PARV4 infections with those of other respiratory virus infections, by evaluating diagnostic samples referred to the Specialist Virology Laboratory (SVL) at the Royal Infirmary of Edinburgh (Edinburgh, United Kingdom)

MethodsAnonymized samples and study subject information were obtained from the respiratory sample archive of the SVL. Samples were screened for HBoV, PARV4, B19, respiratory syncytial virus (RSV), adenoviruses, influenza viruses, and parainfluenza viruses by use of nested polymerase chain reaction

ResultsHBoV infection was detected in 47 (8.2%) of 574 study subjects,&amp;ranking third in prevalence behind RSV infection (15.7%) and adenovirus infection (10.3%). Peak incidences of HBoV were noted among infants and young children (age, 6–24 months) during the midwinter months (December and January) and were specifically associated with lower respiratory tract infections. HBoV infections were frequently accompanied by other respiratory viruses (frequency, 43%), and they were more prevalent among individuals infected with other respiratory viruses (17%), frequently adenovirus or RSV. All respiratory samples were negative for PARV4

ConclusionsIn the present study, HBoV was a frequently detected, potential respiratory pathogen, with a prevalence and an epidemiological profile comparable to those of RSV. Identification of HBoV infections may be clinically important in the future

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<![CDATA[A Comparative Study of Clinical Features and Outcomes in Young and Older Adults with Severe Acute Respiratory Syndrome]]> https://www.researchpad.co/article/N20325ea6-086c-45a0-bc3a-e516606aaec8

Objectives: To determine the clinical presentation, findings, and outcomes of older adults (> 60) with severe acute respiratory syndrome (SARS) and compare these with a control group of younger patients (≤60).

Design: Retrospective cohort study.

Setting: A community‐based, acute hospital in Hong Kong.

Participants: All adult inpatients with a clinical diagnosis of SARS.

Measurements: Clinical presentations, investigations, treatment, and 30‐ and 150‐day mortality.

Results: There were 52 young and 25 older patients with a mean age±standard deviation of 39.5±11.7 and 72.1±7.2, respectively. Fever, chills, and diarrhea were more common in younger patients, whereas decrease in appetite and general condition occurred only in older patients. The prevalence of positive reverse‐transcriptase polymerase chain reaction for SARS‐associated coronavirus (SARS‐CoV) in nasopharyngeal secretions and stool samples was similar in the two groups. The prevalence of positive serological tests for SARS‐CoV was significantly lower in older patients (42% vs 92%, P<.001). This was largely due to incomplete testing in elderly patients. Older patients were more likely to develop secondary nosocomial infection, be admitted to an intensive care unit, and require mechanical ventilation. The cumulative 30‐ and 150‐day mortality rates were 3.8% and 7.6%, respectively, in young patients with SARS and 56% and 60%, respectively, in older patients (P<.001).

Conclusion: Older patients with SARS more often presented with nonspecific symptoms, and the prognosis was poor. Reverse‐transcriptase polymerase chain reaction was useful in diagnosing SARS in older patients, but the role of serological tests in individual elderly is limited.

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