Randomized, Double-Blinded, Placebo-Controlled Phase 2 Trial of an Inactivated Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine in Healthy Adults

Che, Yanchun; Liu, Xiaoqiang; Pu, Yi; Zhou, Meijian; Zhao, Zhihui; Jiang, Ruiju; Yin, Zhifang; Xu, Mingjue; Yin, Qiongzhou; Wang, Jianfeng; Pu, Jing; Zhao, Heng; Zhang, Ying; Wang, Lichun; Jiang, Ya; Jin, Longcun; Zheng, Yefeng; Liao, Yun; Long, Runxiang; Liu, Yu; Cui, Pingfang; Yang, Huijuan; Zhang, Yuehui; Li, Jingyu; Chen, Weiwu; He, Zhanlong; Ma, Kaili; Chen, Hong; Li, Dandan; Jiang, Guorun; Liu, Donglan; Xu, Xingli; Fan, Shengtao; Chen, Cheng; Zhao, Hang; Yang, Jianbo; Li, Yan; Zou, Yanxiang; Zhu, Youshuai; Zhou, Yubin; Guo, Yingqiu; Yang, Ting; Chen, Hongbo; Xie, Zhihui; Li, Changgui; Li, Qihan

doi:10.1093/cid/ciaa1703

Cited by 69 publications

(95 citation statements)

References 7 publications

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“…This work adds to the literature by demonstrating that the FNR of SARS-CoV-2 molecular assays is low [ 1 , 27 , 28 ] and subject to viral load dynamics over time. However, the interpretation of COVID-19 test results should be conducted in the overall context of each patient’s clinical presentation [ 9 , 29 ], with repeat testing advised should post-test probability upon follow-up clinical evaluation remain high.…”

Section: Resultsmentioning

confidence: 80%

“…Data from earlier in the pandemic reported FNRs of up to 30% [ 6 ] with a systematic review on the topic reporting ranges from 2 to 29% [ 2 ]. A large study from New York evaluating the clinical performance of SARS-CoV-2 molecular testing found that on average up to 17% of positives were missed by the first test [ 22 ], while another American study reported a FNR of 3.5% in patients with discordant swab results within a 7-day period [ 1 ]. Two other studies have estimated sensitivities ranging from 89 to 94.6% [ 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

“…Studies of false-negative (FN) results from respiratory samples for SARS-CoV-2 are variable demonstrating FN rates (FNRs) ranging from 1 to 30% [ 1 , 2 ]. FN results can occur for numerous reasons including suboptimal specimen collection, testing too early in the disease process, low analytic sensitivity, inappropriate specimen type, low viral load, or variability in viral shedding [ 3 – 9 ].…”

Section: Introductionmentioning

confidence: 99%

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False negative rate of COVID-19 PCR testing: a discordant testing analysis

Kanji

Zelyas

MacDonald

et al. 2021

Virol J

190

153

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Background COVID-19 is diagnosed via detection of SARS-CoV-2 RNA using real time reverse-transcriptase polymerase chain reaction (rtRT-PCR). Performance of many SARS-CoV-2 rtRT-PCR assays is not entirely known due to the lack of a gold standard. We sought to evaluate the false negative rate (FNR) and sensitivity of our laboratory-developed SARS-CoV-2 rtRT-PCR targeting the envelope (E) and RNA-dependent RNA-polymerase (RdRp) genes. Methods SARS-CoV-2 rtRT-PCR results at the Public Health Laboratory (Alberta, Canada) from January 21 to April 18, 2020 were reviewed to identify patients with an initial negative rtRT-PCR followed by a positive result on repeat testing within 14 days (defined as discordant results). Negative samples from these discordant specimens were re-tested using three alternate rtRT-PCR assays (targeting the E gene and N1/N2 regions of the nucleocapsid genes) to assess for false negative (FN) results. Results During the time period specified, 95,919 patients (100,001 samples) were tested for SARS-CoV-2. Of these, 49 patients were found to have discordant results including 49 positive and 52 negative swabs. Repeat testing of 52 negative swabs found five FNs (from five separate patients). Assuming 100% specificity of the diagnostic assay, the FNR and sensitivity in this group of patients with discordant testing was 9.3% (95% CI 1.5–17.0%) and 90.7% (95% CI 82.6–98.9%) respectively. Conclusions Studies to understand the FNR of routinely used assays are important to confirm adequate clinical performance. In this study, most FN results were due to low amounts of SARS-CoV-2 virus concentrations in patients with multiple specimens collected during different stages of infection. Post-test clinical evaluation of each patient is advised to ensure that rtRT-PCR results are not the only factor in excluding COVID-19.

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Section: Resultsmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

False negative rate of COVID-19 PCR testing: a discordant testing analysis

Kanji

Zelyas

MacDonald

et al. 2021

Virol J

190

153

View full text Add to dashboard Cite

show abstract

“…Results from measles virus and vesicular stomatitis virus (VSV) based vaccine candidates in animal models were also reported (Horner et al, 2020;. Three studies reported preliminary results on the safety and immunogenicity of inactivated COVID-19 vaccines from phase I/II clinical trials (Che et al, 2020;Zhang et al, 2020g). The inactivated vaccines demonstrated acceptable safety profiles and were effective in inducing neutralizing antibodies.…”

Section: Progress Of Covid-19 Vaccine Developmentmentioning

confidence: 99%

Antibody response and therapy in COVID-19 patients: what can be learned for vaccine development?

Zhang

Zhan

et al. 2020

Sci. China Life Sci.

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The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people and caused tremendous morbidity and mortality worldwide. Effective treatment for coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection is lacking, and different therapeutic strategies are under testing. Host humoral and cellular immunity to SARS-CoV-2 infection is a critical determinant for patients’ outcomes. SARS-CoV-2 infection results in seroconversion and production of anti-SARS-CoV-2 antibodies. The antibodies may suppress viral replication through neutralization but might also participate in COVID-19 pathogenesis through a process termed antibody-dependent enhancement. Rapid progress has been made in the research of antibody response and therapy in COVID-19 patients, including characterization of the clinical features of antibody responses in different populations infected by SARS-CoV-2, treatment of COVID-19 patients with convalescent plasma and intravenous immunoglobin products, isolation and characterization of a large panel of monoclonal neutralizing antibodies and early clinical testing, as well as clinical results from several COVID-19 vaccine candidates. In this review, we summarize the recent progress and discuss the implications of these findings in vaccine development.

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“…Through the protocol, we have not seen any COVID-19 cases attributed to AFTs, although we cannot rule out possibilities of asymptomatic cases without repeated PCR tests. The PCR testing at our institution has specificity of 99.9% and false-negative rate of 2.8% [ 3 , 4 ]. When combined with testing at other facilities, they may differ, and infection risk during AFTs may change due to patients from other counties or states.…”

mentioning

confidence: 99%