Opass Putcharoen1, Supaporn Wacharapluesadee2, Wan Ni Chia3, Leilani Paitoonpong1, Chee Wah Tan3, Gompol Suwanpimolkul1, Watsamon Jantarabenjakul4, Chanida Ruchisrisarod2, Phanni Wanthong2, Jiratchaya Sophonphan5, Pajaree Chariyavilaskul6,7, Lin-Fa Wang3, Thiravat Hemachudha2. 1. Division of Infectious Diseases, Department of Medicine, Faculty of Medicine, Thai Red Cross Emerging Infectious Diseases Clinical Centre, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand. 2. Thai Red Cross Emerging Infectious Diseases Health Science Centre World Health Organization Collaborating Centre for Research and Training on Viral Zoonoses, King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 3. Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore. 4. Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine, Thai Red Cross Emerging Infectious Diseases Clinical Centre, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand. 5. The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Bangkok, Thailand. 6. Clinical Pharmacokinetics and Pharmacogenomics Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 7. Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Abstract
BACKGROUND: The presence of neutralizing antibodies (NAbs) is an indicator of protective immunity for most viral infections. A newly developed surrogate viral neutralization assay (sVNT) offers the ability to detect total receptor binding domain-targeting NAbs in an isotype-independent manner, increasing the test sensitivity. Thus, specimens with low IgM/ IgG antibody levels showed strong neutralization activity in sVNT. METHODS: This study aimed to measure the %inhibition of NAbs measured by sVNT in PCR-confirmed COVID-19 patients. The sensitivity of sVNT for the diagnosis of SARS-CoV-2 infection and its kinetics were determined. RESULTS: Ninety-seven patients with PCR-confirmed SARS-CoV-2 infection were included in this study. Majority of the patients were 21-40 years old (67%) and 63% had mild symptoms. The sensitivity of sVNT for the diagnosis of SARS-CoV-2 infection was 99% (95% confidence interval (CI) 94.4-100%) and the specificity was 100% (95% CI 98.3-100%). The negative predictive value of sVNT from the samples collected before and after 7 days of symptom onset was 99.5% (95% CI 97.4-100%) and 100% (95% CI 93.8-100%), respectively. The level of inhibition at days 8-14 were significantly higher than days 0-7 (p<0.001). The median %inhibition values by severity of COVID-19 symptoms were 79.9% (interquartile range (IQR) 49.7-91.8%); 89.0% (IQR 71.2-92.4%); and 86.6% (IQR 69.5-92.8%), for mild, moderate and severe/critical symptoms respectively. The median level of sVNT %inhibition of severe was significantly higher than the mild group (p = 0.05). CONCLUSION: The sVNT is a practical and robust serological test for SARS-CoV-2 infection and does not require specialized biosafety containment. It can be used clinically to aid diagnosis in both early and late infection especially in cases when the real-time RT-PCR results in weakly negative or weakly positive, and to determine the protective immune response from SARS-CoV-2 infection in patients.
BACKGROUND: The presence of neutralizing antibodies (NAbs) is an indicator of protective immunity for most viral infections. A newly developed surrogate viral neutralization assay (sVNT) offers the ability to detect total receptor binding domain-targeting NAbs in an isotype-independent manner, increasing the test sensitivity. Thus, specimens with low IgM/ IgG antibody levels showed strong neutralization activity in sVNT. METHODS: This study aimed to measure the %inhibition of NAbs measured by sVNT in PCR-confirmed COVID-19 patients. The sensitivity of sVNT for the diagnosis of SARS-CoV-2 infection and its kinetics were determined. RESULTS: Ninety-seven patients with PCR-confirmed SARS-CoV-2 infection were included in this study. Majority of the patients were 21-40 years old (67%) and 63% had mild symptoms. The sensitivity of sVNT for the diagnosis of SARS-CoV-2 infection was 99% (95% confidence interval (CI) 94.4-100%) and the specificity was 100% (95% CI 98.3-100%). The negative predictive value of sVNT from the samples collected before and after 7 days of symptom onset was 99.5% (95% CI 97.4-100%) and 100% (95% CI 93.8-100%), respectively. The level of inhibition at days 8-14 were significantly higher than days 0-7 (p<0.001). The median %inhibition values by severity of COVID-19 symptoms were 79.9% (interquartile range (IQR) 49.7-91.8%); 89.0% (IQR 71.2-92.4%); and 86.6% (IQR 69.5-92.8%), for mild, moderate and severe/critical symptoms respectively. The median level of sVNT %inhibition of severe was significantly higher than the mild group (p = 0.05). CONCLUSION: The sVNT is a practical and robust serological test for SARS-CoV-2 infection and does not require specialized biosafety containment. It can be used clinically to aid diagnosis in both early and late infection especially in cases when the real-time RT-PCR results in weakly negative or weakly positive, and to determine the protective immune response from SARS-CoV-2 infection in patients.
Authors: Safiya Richardson; Jamie S Hirsch; Mangala Narasimhan; James M Crawford; Thomas McGinn; Karina W Davidson; Douglas P Barnaby; Lance B Becker; John D Chelico; Stuart L Cohen; Jennifer Cookingham; Kevin Coppa; Michael A Diefenbach; Andrew J Dominello; Joan Duer-Hefele; Louise Falzon; Jordan Gitlin; Negin Hajizadeh; Tiffany G Harvin; David A Hirschwerk; Eun Ji Kim; Zachary M Kozel; Lyndonna M Marrast; Jazmin N Mogavero; Gabrielle A Osorio; Michael Qiu; Theodoros P Zanos Journal: JAMA Date: 2020-05-26 Impact factor: 56.272
Authors: Elitza S Theel; Patricia Slev; Sarah Wheeler; Marc Roger Couturier; Susan J Wong; Kamran Kadkhoda Journal: J Clin Microbiol Date: 2020-07-23 Impact factor: 5.948
Authors: Kizzmekia S Corbett; Barbara Flynn; Kathryn E Foulds; Joseph R Francica; Seyhan Boyoglu-Barnum; Anne P Werner; Britta Flach; Sarah O'Connell; Kevin W Bock; Mahnaz Minai; Bianca M Nagata; Hanne Andersen; David R Martinez; Amy T Noe; Naomi Douek; Mitzi M Donaldson; Nadesh N Nji; Gabriela S Alvarado; Darin K Edwards; Dillon R Flebbe; Evan Lamb; Nicole A Doria-Rose; Bob C Lin; Mark K Louder; Sijy O'Dell; Stephen D Schmidt; Emily Phung; Lauren A Chang; Christina Yap; John-Paul M Todd; Laurent Pessaint; Alex Van Ry; Shanai Browne; Jack Greenhouse; Tammy Putman-Taylor; Amanda Strasbaugh; Tracey-Ann Campbell; Anthony Cook; Alan Dodson; Katelyn Steingrebe; Wei Shi; Yi Zhang; Olubukola M Abiona; Lingshu Wang; Amarendra Pegu; Eun Sung Yang; Kwanyee Leung; Tongqing Zhou; I-Ting Teng; Alicia Widge; Ingelise Gordon; Laura Novik; Rebecca A Gillespie; Rebecca J Loomis; Juan I Moliva; Guillaume Stewart-Jones; Sunny Himansu; Wing-Pui Kong; Martha C Nason; Kaitlyn M Morabito; Tracy J Ruckwardt; Julie E Ledgerwood; Martin R Gaudinski; Peter D Kwong; John R Mascola; Andrea Carfi; Mark G Lewis; Ralph S Baric; Adrian McDermott; Ian N Moore; Nancy J Sullivan; Mario Roederer; Robert A Seder; Barney S Graham Journal: N Engl J Med Date: 2020-07-28 Impact factor: 91.245
Authors: Amin Addetia; Katharine H D Crawford; Adam Dingens; Haiying Zhu; Pavitra Roychoudhury; Meei-Li Huang; Keith R Jerome; Jesse D Bloom; Alexander L Greninger Journal: J Clin Microbiol Date: 2020-10-21 Impact factor: 5.948
Authors: Katherine Bond; Suellen Nicholson; Seok Ming Lim; Theo Karapanagiotidis; Eloise Williams; Douglas Johnson; Tuyet Hoang; Cheryll Sia; Damian Purcell; Francesca Mordant; Sharon R Lewin; Mike Catton; Kanta Subbarao; Benjamin P Howden; Deborah A Williamson Journal: J Infect Dis Date: 2020-09-14 Impact factor: 5.226
Authors: José Javier Morales-Núñez; José Francisco Muñoz-Valle; Paola Carolina Torres-Hernández; Jorge Hernández-Bello Journal: Vaccines (Basel) Date: 2021-11-23
Authors: Jacob T Heggestad; Rhett J Britton; David S Kinnamon; Simone A Wall; Daniel Y Joh; Angus M Hucknall; Lyra B Olson; Jack G Anderson; Anna Mazur; Cameron R Wolfe; Thomas H Oguin; Bruce A Sullenger; Thomas W Burke; Bryan D Kraft; Gregory D Sempowski; Christopher W Woods; Ashutosh Chilkoti Journal: Sci Adv Date: 2021-12-03 Impact factor: 14.957
Authors: Denis E Kolesov; Maria V Sinegubova; Lutsia K Dayanova; Inna V Dolzhikova; Ivan I Vorobiev; Nadezhda A Orlova Journal: Diagnostics (Basel) Date: 2022-02-03