scholarly journals Methods to Measure Antibody Neutralization of Live Human Coronavirus OC43

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2075
Author(s):  
Jim Boonyaratanakornkit ◽  
Anton M. Sholukh ◽  
Matthew Gray ◽  
Emily L. Bossard ◽  
Emily S. Ford ◽  
...  

The human Betacoronavirus OC43 is a common cause of respiratory viral infections in adults and children. Lung infections with OC43 are associated with mortality, especially in hematopoietic stem cell transplant recipients. Neutralizing antibodies play a major role in protection against many respiratory viral infections, but to date a live viral neutralization assay for OC43 has not been described. We isolated a human monoclonal antibody (OC2) that binds to the spike protein of OC43 and neutralizes the live virus derived from the original isolate of OC43. We used this monoclonal antibody to develop and test the performance of two readily accessible in vitro assays for measuring antibody neutralization, one utilizing cytopathic effect and another utilizing an ELISA of infected cells. We used both methods to measure the neutralizing activity of the OC2 monoclonal antibody and of human plasma. These assays could prove useful for studying humoral responses to OC43 and cross-neutralization with other medically important betacoronaviruses.

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S319-S319
Author(s):  
Shashank S Ghantoji ◽  
Siddharth Karanth ◽  
Lynn El Haddad ◽  
Anne Park ◽  
David Lairson ◽  
...  

Abstract Background Respiratory syncytial virus (RSV), parainfluenza virus (PIV) and influenza virus (Flu) are common respiratory viral infections (RVIs) implicated in hematopoietic stem cell transplant (HSCT) recipients. Despite their possible association with high rates of pneumonia and mortality, their clinical and economic burden has not been well studied. Methods HSCT recipients with documented RVI who were treated at our institution between September 2012 and October 2015 were included in the study. We used Vizient (formerly University Health Consortium) clinical database to collect and compare total costs, including length of stay, ICU admission rates, intravenous immunoglobulin use, steroid use, and mortality rates among RVIs in HSCT recipients. Encounter-specific demographics, risk factors, underlying cancer, and outcomes were also collected. Multiple linear regression analyses were applied to identify predictors of higher total cost associated with RVI in HSCT recipients at MD Anderson. Results Average total cost per encounter was $49,371 for RSV, $29,679 for PIV, and $15,077 for Flu. A total of 1,636 hospitalization days (d) were attributed to these RVIs with an average of 7 d per RSV, 8 d per PIV, and 5 d for Flu infection. The average ICU admission rate was 12% for RSV, 9% for PIV, and 4% for Flu. Around 11% of total RVI encounters had active graft-vs.-host disease at the time of their RVI. Out of the patients with upper respiratory infection, 20% RSV, 44% PIV, and 21% Flu progressed to pneumonia during the 28 d of the study period. Of the 246 total RVI encounters, overall all-cause mortality rate was 6% (RSV: 8% [8/98], PIV: 1% [1/70] and Flu: 8% [6/78]). Length of stay, ICU admission, and receiving intravenous immunoglobulin were strong predictors of higher cost for all RVIs. Conclusion This study underscores the significant impact of RVIs in terms of economic and clinical burden in HSCT recipients. Major differences in total costs per encounter across the three RVIs were observed. This cost and clinical data may be helpful for future cost effectiveness studies in this population. Disclosures All authors: No reported disclosures.


2015 ◽  
Vol 59 (7) ◽  
pp. 3718-3725 ◽  
Author(s):  
Amy E. Caruso Brown ◽  
Mindy N. Cohen ◽  
Suhong Tong ◽  
Rebecca S. Braverman ◽  
James F. Rooney ◽  
...  

ABSTRACTChildren undergoing hematopoietic stem cell transplantation (HSCT) are at risk for life-threatening viral infections. Cidofovir is often used as a first-line agent for adenovirus infections, despite the absence of randomized controlled trials with HSCT patients, and as a second-line agent for resistant herpesvirus infections. The frequency and severity of adverse effects, particularly nephrotoxicity, in pediatric HSCT recipients are unclear, and pharmacokinetics (PK) of cidofovir in children have not previously been reported. This study was an open-label, nonrandomized, single-dose pilot study to determine the safety and PK of cidofovir in pediatric HSCT recipients with symptomatic adenovirus, nucleoside-resistant cytomegalovirus (CMV) or herpes simplex virus (HSV), and/or human papovavirus infections. Subsequent dosing and frequency were determined by clinical response and side effects, as assessed by the treating physician. Blood and urine samples were obtained from patients for PK studies and assessment of toxicity and virologic response. Twelve patients were enrolled (median age, 9 years; 33.5 days posttransplantation). Four of seven patients with adenovirus infection were successfully treated and eventually cleared their infections. Four of twelve patients died of disseminated viral disease and multiorgan failure. Two of twelve patients had evidence of acute kidney injury after the first dose, and one of these patients developed chronic kidney disease; two other patients developed late nephrotoxicity. The mean drug half-life was 9.5 h. There was no correlation between nephrotoxicity and plasma maximum concentration, clearance, or half-life. PK were similar to those reported for adults, although the drug half-life was significantly longer than that for adults. Cidofovir was well tolerated in the majority of patients. However, effective therapeutic strategies are urgently needed to support patients until immune reconstitution is achieved.


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