PDF(Pubmed)
Abstract：
UNASSIGNED: Virologic determinants of seroconversion to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were defined in a post hoc analysis of prospectively studied vaccine- and infection-naïve individuals at high risk for coronavirus disease 2019 (COVID-19).
UNASSIGNED: This phase 3 COVID-19 prevention trial (NCT04452318) with casirivimab and imdevimab was conducted in July 2020-February 2021, before widespread vaccine availability. Placebo-treated participants who were uninfected (SARS-CoV-2 quantitative reverse transcription polymerase chain reaction [RT-qPCR] negative) and seronegative were assessed weekly for 28 days (efficacy assessment period [EAP]) for COVID-19 symptoms and SARS-CoV-2 infection by RT-qPCR of nasopharyngeal swab samples and for serostatus by antinucleocapsid immunoglobulin (Ig) G. Regression-based modeling, including causal mediation analysis, estimated the effects of viral load on seroconversion.
UNASSIGNED: Of 157/1069 (14.7%) uninfected and seronegative (for antispike IgG, antispike IgA, and antinucleocapsid IgG) participants who became infected during the EAP, 105 (65%) seroconverted. The mean (SD) maximum viral load of seroconverters was 7.23 (1.68) log10 copies/mL vs 4.8 (2.2) log10 copies/mL in those who remained seronegative; viral loads of ∼6.0 log10 copies/mL better predicted seroconversion. The mean of the maximum viral load was 7.11 log10 copies/mL in symptomatic participants vs 5.58 log10 copies/mL in asymptomatic participants. The mean duration of detectable viral load was longer in seroconverted vs seronegative participants: 3.24 vs 1.63 weeks.
UNASSIGNED: Maximum SARS-CoV-2 viral load is a major driver of seroconversion and symptomatic COVID-19, with high viral loads (∼6.0 log10 copies/mL) better predicting seroconversion. Serology underestimates infection rates, incidence, and prevalence of SARS-CoV-2 infection.
UNASSIGNED: This phase 3 COVID-19 prevention trial (NCT04452318) with casirivimab and imdevimab was conducted in July 2020-February 2021, before widespread vaccine availability. Placebo-treated participants who were uninfected (SARS-CoV-2 quantitative reverse transcription polymerase chain reaction [RT-qPCR] negative) and seronegative were assessed weekly for 28 days (efficacy assessment period [EAP]) for COVID-19 symptoms and SARS-CoV-2 infection by RT-qPCR of nasopharyngeal swab samples and for serostatus by antinucleocapsid immunoglobulin (Ig) G. Regression-based modeling, including causal mediation analysis, estimated the effects of viral load on seroconversion.
UNASSIGNED: Of 157/1069 (14.7%) uninfected and seronegative (for antispike IgG, antispike IgA, and antinucleocapsid IgG) participants who became infected during the EAP, 105 (65%) seroconverted. The mean (SD) maximum viral load of seroconverters was 7.23 (1.68) log10 copies/mL vs 4.8 (2.2) log10 copies/mL in those who remained seronegative; viral loads of ∼6.0 log10 copies/mL better predicted seroconversion. The mean of the maximum viral load was 7.11 log10 copies/mL in symptomatic participants vs 5.58 log10 copies/mL in asymptomatic participants. The mean duration of detectable viral load was longer in seroconverted vs seronegative participants: 3.24 vs 1.63 weeks.
UNASSIGNED: Maximum SARS-CoV-2 viral load is a major driver of seroconversion and symptomatic COVID-19, with high viral loads (∼6.0 log10 copies/mL) better predicting seroconversion. Serology underestimates infection rates, incidence, and prevalence of SARS-CoV-2 infection.
摘要：
■血清转化为严重急性呼吸道综合征冠状病毒2(SARS-CoV-2)感染的病毒学决定因素是在对2019年冠状病毒疾病高危人群(COVID-19)进行前瞻性研究的疫苗和未感染个体的事后分析中定义的。
■这项使用casirivimab和imdevimab的COVID-19预防试验（NCT04452318）于2020年7月至2021年2月进行，在广泛的疫苗供应之前。每周对未感染（SARS-CoV-2定量逆转录聚合酶链反应[RT-qPCR]阴性）和血清阴性的安慰剂治疗参与者进行28天（疗效评估期[EAP]）的COVID-19症状和SARS-CoV-2感染通过RT-qPCR对鼻咽拭子样本进行RT-qPCR和抗核衣壳免疫球蛋白（Ig）G的血清状态评估。基于回归的建模，包括因果调解分析，估计病毒载量对血清转化的影响。
■在未感染和血清阴性的157/1069（14.7％）中（对于抗标IgG，抗刺药IgA,和抗核衣壳IgG）在EAP期间感染的参与者，105(65%)血清转化。血清转化者的平均（SD）最大病毒载量为7.23（1.68）log10拷贝/mL与4.8（2.2）log10拷贝/mL在那些保持血清阴性的人中；~6.0log10拷贝/mL的病毒载量更好地预测血清转化。在有症状的参与者中，最大病毒载量的平均值为7.11log10拷贝/mL，在无症状的参与者中为5.58log10拷贝/mL。血清转化和血清阴性参与者的平均可检测病毒载量持续时间更长：3.24vs1.63周。
■最大SARS-CoV-2病毒载量是血清转换和有症状的COVID-19的主要驱动因素，高病毒载量（约6.0log10拷贝/mL）可以更好地预测血清转换。血清学低估了感染率,发病率,和SARS-CoV-2感染的患病率。
■这项使用casirivimab和imdevimab的COVID-19预防试验（NCT04452318）于2020年7月至2021年2月进行，在广泛的疫苗供应之前。每周对未感染（SARS-CoV-2定量逆转录聚合酶链反应[RT-qPCR]阴性）和血清阴性的安慰剂治疗参与者进行28天（疗效评估期[EAP]）的COVID-19症状和SARS-CoV-2感染通过RT-qPCR对鼻咽拭子样本进行RT-qPCR和抗核衣壳免疫球蛋白（Ig）G的血清状态评估。基于回归的建模，包括因果调解分析，估计病毒载量对血清转化的影响。
■在未感染和血清阴性的157/1069（14.7％）中（对于抗标IgG，抗刺药IgA,和抗核衣壳IgG）在EAP期间感染的参与者，105(65%)血清转化。血清转化者的平均（SD）最大病毒载量为7.23（1.68）log10拷贝/mL与4.8（2.2）log10拷贝/mL在那些保持血清阴性的人中；~6.0log10拷贝/mL的病毒载量更好地预测血清转化。在有症状的参与者中，最大病毒载量的平均值为7.11log10拷贝/mL，在无症状的参与者中为5.58log10拷贝/mL。血清转化和血清阴性参与者的平均可检测病毒载量持续时间更长：3.24vs1.63周。
■最大SARS-CoV-2病毒载量是血清转换和有症状的COVID-19的主要驱动因素，高病毒载量（约6.0log10拷贝/mL）可以更好地预测血清转换。血清学低估了感染率,发病率,和SARS-CoV-2感染的患病率。
