Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection and analysis of IgG non-responders.

Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection and analysis of IgG non-responders.
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DOI:
10.1371/journal.pone.0241104
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发表时间:
2020
期刊:
影响因子:
3.7
通讯作者:
Gisslén M
Gisslén M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Marklund E;Leach S;Axelsson H;Nyström K;Norder H;Bemark M;Angeletti D;Lundgren A;Nilsson S;Andersson LM;Yilmaz A;Lindh M;Liljeqvist JÅ;Gisslén M

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为了准确解释COVID-19血清阳性率调查,必须了解血清igg对SARS-CoV-2的反应,并更好地了解未进行血清转化的患者。本研究旨在描述严重和轻度COVID-19患者队列中血清igg对SARS-CoV-2的反应,包括对症状出现后90天以上血清阴性的患者的扩展研究。使用两种经临床验证且广泛使用的商用血清学检测方法(Architect, Abbott Laboratories和iFlash 1800, YHLO)对sars - cov -2特异性IgG抗体水平进行量化,检测针对刺突和核衣壳蛋白的抗体。纳入47例患者(平均年龄49岁,女性38%)。所有(15/15)重症患者和29/32(90.6%)轻症患者血清中均出现sars - cov -2特异性IgG抗体。症状严重的患者到血清转化的时间明显短于症状轻微的患者(中位11天vs. 22天,P = 0.04)。三名患者在bbbb90天后没有检测到IgG反应,所有患者都有可检测到的病毒中和抗体,其中两名患者通过内部检测检测到刺突蛋白受体结合域特异性IgG。在随访期间保留抗体滴度,所有血清转化的患者,无论症状的严重程度如何,在症状出现后75天仍可检测到IgG水平。与症状较轻的患者相比,重症COVID-19患者血清转化更早,并且出现更高浓度的sars - cov -2特异性IgG。在那些没有检测到IgG抗体的患者中,所有患者都有可检测到的病毒中和抗体,表明免疫。我们的研究结果表明,并非所有COVID-19患者使用两种经过验证的商业临床方法都能检测到IgG,即使随着时间的推移,这对于解释COVID-19血清阳性率调查至关重要。
To accurately interpret COVID-19 seroprevalence surveys, knowledge of serum-IgG responses to SARS-CoV-2 with a better understanding of patients who do not seroconvert, is imperative. This study aimed to describe serum-IgG responses to SARS-CoV-2 in a cohort of patients with both severe and mild COVID-19, including extended studies of patients who remained seronegative more than 90 days post symptom onset. SARS-CoV-2-specific IgG antibody levels were quantified using two clinically validated and widely used commercial serological assays (Architect, Abbott Laboratories and iFlash 1800, YHLO), detecting antibodies against the spike and nucleocapsid proteins. Forty-seven patients (mean age 49 years, 38% female) were included. All (15/15) patients with severe symptoms and 29/32 (90.6%) patients with mild symptoms of COVID-19 developed SARS-CoV-2-specific IgG antibodies in serum. Time to seroconversion was significantly shorter (median 11 vs. 22 days, P = 0.04) in patients with severe compared to mild symptoms. Of the three patients without detectable IgG-responses after >90 days, all had detectable virus-neutralizing antibodies and in two, spike-protein receptor binding domain-specific IgG was detected with an in-house assay. Antibody titers were preserved during follow-up and all patients who seroconverted, irrespective of the severity of symptoms, still had detectable IgG levels >75 days post symptom onset. Patients with severe COVID-19 both seroconvert earlier and develop higher concentrations of SARS-CoV-2-specific IgG than patients with mild symptoms. Of those patients who not develop detectable IgG antibodies, all have detectable virus-neutralizing antibodies, suggesting immunity. Our results showing that not all COVID-19 patients develop detectable IgG using two validated commercial clinical methods, even over time, are vital for the interpretation of COVID-19 seroprevalence surveys.
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